bluuebunny/crossref_metadata_2025 huggingface dataset:
Age, Growth, Survival, and Maturity of Lake Trout Morphotypes in Lake Mistassini, Quebec
Authors: Hansen Michael J. , Nate Nancy A. , Krueger Charles C. , Zimmerman Mara S. , Kruckman Hanna G. , Taylor William W.
Published: October 2012

Life history characteristics (age, growth, survival, and maturity) were compared between the deepwater “humper” and shallow‐water “lean” forms of lake troutSalvelinus namaycushin Lake Mistassini, Quebec, to determine whether the two morphotypes may represent resource polymorphism. Lake trout were sampled using graded‐mesh (range = 51–114 mm stretch) gill nets set in deep and shallow waters. Humpers were typically caught in deep waters (>50 m) and averaged 474 mm TL (range = 389–616 mm) and 852 g in weight (range = 470–1,710 g), whereas leans were typically caught in shallow waters (<50 m) and averaged 525 mm TL (range = 301–865 mm) and 1,210 g in weight (range = 200–6,500 g). Humpers and leans did not differ in weight–length relationships and grew slimmer with length over a common TL range (389–616 mm). Average age of humpers was 27 years (range = 13–49 years); average age of leans was 21 years (range = 6–42 years). The two forms did not differ in total annual mortality (A) of fish older than 17 years, the first age beyond which numbers declined with age for both morphs (A= 5.1%; 95% confidence interval = 2.4–7.8%). Humpers grew slower (annual growth rateω= 53 mm/year) than leans (ω= 68 mm/year) and to a shorter mean asymptotic length (L∞= 514 mm) than leans (L∞= 605 mm). Mature humpers (mean TL = 475 mm, SE = 9.0;N= 58) were shorter on average than mature leans (mean TL = 539 mm, SE = 8.5;N= 65); mature humpers (mean age = 27 years, SE = 1.0;N= 56) were also older on average than mature leans (mean age = 23 years, SE = 0.98;N= 61). We conclude that lean and humper forms of lake trout in Lake Mistassini differed in age, growth, and maturity; this is consistent with the resource polymorphism that has been observed for other lake trout populations and other char species.
A Comparison of Early Development between a Domesticated Stock of Coho Salmon and Its Parental Stock
Authors: Neely Kathleen G. , Myers James M. , Hard Jeffrey J.
Published: October 2012

We compared the rate of early development and yolk conversion efficiency in a domesticated stock of coho salmon Oncorhynchus kisutch that had been selected for improved growth to pan size (350 g) over 18 generations with that of its hatchery‐origin unselected parental stock. Fish from both the domesticated stock and the parental stock were spawned and incubated under similar conditions. The domesticated fish produced significantly smaller eggs, reached blastopore closure sooner, and utilized their yolk store more efficiently than the parental stock. Because we were concerned that egg size may have confounded the results of the blastopore closure portion of the experiment, we repeated the experiment using eggs of sizes different from those of the domesticated stock. We determined that the rate of early embryonic development to blastopore closure was strongly influenced by egg size, an influence that probably confounded our stock comparison. In contrast, comparisons of later embryonic growth rates show a clear distinction between the domesticated stock and parental stock, the domesticated stock exhibiting a growth rate significantly faster than that of parental stock for exogenous feeding.
Effects of Garlic and Ginger Oils on Hematological and Biochemical Variables of Sea Bass Dicentrarchus labrax
Authors: Yılmaz Sevdan , Ergün Sebahattin
Published: October 2012

This study was conducted to investigate the effects of garlic and ginger oils on hematological and biochemical health characteristics of sea bass Dicentrarchus labrax. Fish were exposed to garlic oil (0.01 or 0.02 mL/L), ginger oil (0.01 or 0.02 mL/L), or a combination of the two oils (each oil at a concentration of 0.005 or 0.01 mL/L) for 96 h via bath immersion. Results showed that the red blood cell count, hematocrit (%), hemoglobin (Hb) concentration (g/dL), mean corpuscular volume (μm3), mean corpuscular Hb (pg), and mean corpuscular Hb concentration (%) were not significantly affected by herb oil exposure. However, some changes in biochemical variables were observed. Sea bass exposed to the 0.005-mL/L garlic oil–ginger oil mixture exhibited a significant increase in serum glucose. Serum total protein and albumin levels decreased in sea bass that were exposed to a garlic oil–ginger oil mixture (0.005 or 0.01 mL/L) or to garlic oil at 0.02 mL/L. Serum globulin levels decreased and triglyceride levels increased in sea bass exposed to 0.02-mL/L garlic oil or to the 0.01-mL/L mixture. The serum lipase level decreased and the cholesterol level increased in fish that were exposed to 0.02-mL/L garlic oil. In summary, ginger oil at 0.01–0.02 mL/L can be used without negative effects, while the garlic oil or garlic oil–ginger oil mixture should be applied at a concentration below 0.005 mL/L for bath immersion of sea bass. This is the first study to examine how garlic oil and ginger oil exposure via bath immersion affects the hematological and biochemical status of sea bass.

Received March 19, 2012; accepted July 2, 2012
EUROSCEPTICISM AND NEIGHBOURHOOD PEACE
Authors: McMahon Richard
Published: October 2012

This article argues that the exceptionally complex spatial organisation of integration is shaped by spatial patterns of socio-cultural difference and similarity which emerge over the course of history. I outline two interacting socio-cultural factors that help shape the spatial patterns of integration: the international relations culture of demilitarised relations between neighbouring countries and northern Euroscepticism. I show that these have different historically evolving spatial patterns, which affect how specific regions and countries engage with integration. I propose that Europe's spatially differentiated integration and weak collective identity are increasingly bringing this connection between culture, geography and politics to prominence. This is rarely noticed however, because the centrality of collective identity in defining the geography of nations has made it the main focus of academic study and political speculation. My approach makes Europe's historical geography an ‘actor’ in the spatial patterning of integration. However the complexity of interacting historical factors and continuous historical change differentiate this approach from essentialist and deterministic theories of historical continuities in the EU's geography.
Thermistor behaviour and electric conduction analysis of Ni-doped niobate ferroelectric: the role of multiple β parameters
Authors: Lanfredi Silvania , Palacio Gustavo , Bellucci Felipe S , Colin Claire V , Nobre Marcos A L
Published: October 2012

A new engineered non-stoichiometric niobate ceramic with a tetragonal tungsten bronze (TTB)-type structure is prepared by non-isovalent substitution at the niobium backbone. The compound's formula is KSr2(Ni0.75Nb4.25)O15−δ, with space group equal toP4bm(#100), a polar group. Electrical properties of this new ferroelectric-semiconductor ceramic are investigated by impedance spectroscopy in the temperature range from 453 up to 953 K. The curve of the resistance as a function of temperature presents further characteristics of a temperature sensor with a negative temperature coefficient (NTC). At high temperatures, the analysis of electrical parameters shows an NTC behaviour ceramic with three distinct thermistor characteristic parameters,β. The values of theβparameter change from 9.82 × 103to 1.29 × 104 K, while the temperature coefficient of resistanceαchanges from −0.047 to −0.023 K−1. The NTC behaviour of KSr2(Ni0.75Nb4.25)O15−δis compared with the behaviour of some dielectric and other ferroelectric semiconductors.βdependence with dc or the ac conductivity mechanism and its correlation withβquality are discussed.
Occurrence and Distribution of Iris yellow spot virus on Onion in Mauritius
Authors: Lobin K. , Pappu H. R. , Benimadhu S. P.
Published: October 2012

Iris yellow spot virus (IYSV), a damaging viral pathogen of onion, was reported for the first time on onion in Mauritius in 2008. A survey was undertaken from 2008 to 2010 to determine the status of the virus in the major onion-growing localities. The disease was found to be prevalent in the east, southeast, south and west of the island in bulb and seed production stands. The high incidence of IYSV in onion fields in Mauritius shows the need for developing integrated management strategies to reduce its negative impact.

Accepted for publication 26 July 2012. Published 26 August 2012.
Pythium Root Rot of Flue-Cured Tobacco Seedlings Produced in Greenhouses: Factors Associated with its Occurrence and Chemical Control
Authors: Gutiérrez Walter , Melton Tom , Mila Asimina
Published: October 2012

Pythium root rot is an economically important disease of tobacco seedlings produced in greenhouses. In a survey conducted in 1998 and 1999, fivePythium species were found to cause Pythium root rot symptoms in tobacco seedlings. In pathogenicity studies the most aggressive species were Pythium volutum and P. myriotylum, although these were not the most frequently isolated species. We conducted studies with potting media from different commercial sources. Media were not found to be a source of primary inoculum for the disease in those studies. Infested trays had the potential to carry inoculum from one season to the next. The fungicides etridiazole, mefenoxam, and azoxystrobin along with acibenzolar-S-methyl and Joy detergent were evaluated for controlling Pythium root rot. Etridiazole and azoxystrobin applied to the float water provided the best control.

Accepted for publication 20 July 2012. Published 25 September 2012.
Warming reduces the growth and diversity of biological soil crusts in a semi-arid environment: implications for ecosystem structure and functioning
Authors: Escolar Cristina , Martínez Isabel , Bowker Matthew A. , Maestre Fernando T.
Published: October 2012

Biological soil crusts (BSCs) are key biotic components of dryland ecosystems worldwide that control many functional processes, including carbon and nitrogen cycling, soil stabilization and infiltration. Regardless of their ecological importance and prevalence in drylands, very few studies have explicitly evaluated how climate change will affect the structure and composition of BSCs, and the functioning of their constituents. Using a manipulative experiment conducted over 3 years in a semi-arid site from central Spain, we evaluated how the composition, structure and performance of lichen-dominated BSCs respond to a 2.4°C increase in temperature, and to an approximately 30 per cent reduction of total annual rainfall. In areas with well-developed BSCs, warming promoted a significant decrease in the richness and diversity of the whole BSC community. This was accompanied by important compositional changes, as the cover of lichens suffered a substantial decrease with warming (from 70 to 40% on average), while that of mosses increased slightly (from 0.3 to 7% on average). The physiological performance of the BSC community, evaluated using chlorophyll fluorescence, increased with warming during the first year of the experiment, but did not respond to rainfall reduction. Our results indicate that ongoing climate change will strongly affect the diversity and composition of BSC communities, as well as their recovery after disturbances. The expected changes in richness and composition under warming could reduce or even reverse the positive effects of BSCs on important soil processes. Thus, these changes are likely to promote an overall reduction in ecosystem processes that sustain and control nutrient cycling, soil stabilization and water dynamics.
Hydrologic variability in dryland regions: impacts on ecosystem dynamics and food security
Authors: D'Odorico Paolo , Bhattachan Abinash
Published: October 2012

Research on ecosystem and societal response to global environmental change typically considers the effects of shifts in mean climate conditions. There is, however, some evidence of ongoing changes also in the variance of hydrologic and climate fluctuations. A relatively high interannual variability is a distinctive feature of the hydrologic regime of dryland regions, particularly at the desert margins. Hydrologic variability has an important impact on ecosystem dynamics, food security and societal reliance on ecosystem services in water-limited environments. Here, we investigate some of the current patterns of hydrologic variability in drylands around the world and review the major effects of hydrologic fluctuations on ecosystem resilience, maintenance of biodiversity and food security. We show that random hydrologic fluctuations may enhance the resilience of dryland ecosystems by obliterating bistable deterministic behaviours and threshold-like responses to external drivers. Moreover, by increasing biodiversity and the associated ecosystem redundancy, hydrologic variability can indirectly enhance post-disturbance recovery, i.e. ecosystem resilience.
Impact of grazing intensity on seasonal variations in soil organic carbon and soil CO
2
efflux in two semiarid grasslands in southern Botswana
Authors: Thomas Andrew D.
Published: October 2012

Biological soil crusts (BSCs) are an important source of organic carbon, and affect a range of ecosystem functions in arid and semiarid environments. Yet the impact of grazing disturbance on crust properties and soil CO
2
efflux remain poorly studied, particularly in African ecosystems. The effects of burial under wind-blown sand, disaggregation and removal of BSCs on seasonal variations in soil CO
2
efflux, soil organic carbon, chlorophyll
a
and scytonemin were investigated at two sites in the Kalahari of southern Botswana. Field experiments were employed to isolate CO
2
efflux originating from BSCs in order to estimate the C exchange within the crust. Organic carbon was not evenly distributed through the soil profile but concentrated in the BSC. Soil CO
2
efflux was higher in Kalahari Sand than in calcrete soils, but rates varied significantly with seasonal changes in moisture and temperature. BSCs at both sites were a small net sink of C to the soil. Soil CO
2
efflux was significantly higher in sand soils where the BSC was removed, and on calcrete where the BSC was buried under sand. The BSC removal and burial under sand also significantly reduced chlorophyll
a
, organic carbon and scytonemin
.
Disaggregation of the soil crust, however, led to increases in chlorophyll
a
and organic carbon. The data confirm the importance of BSCs for C cycling in drylands and indicate intensive grazing, which destroys BSCs through trampling and burial, will adversely affect C sequestration and storage. Managed grazing, where soil surfaces are only lightly disturbed, would help maintain a positive carbon balance in African drylands.
Primer design for identifying economically important Liriomyza species (Diptera: Agromyzidae) by multiplex PCR
Authors: Nakamura Shigeo , Masuda Toshio , Mochizuki Atsushi , Konishi Kazuhiko , Tokumaru Susumu , Ueno Keiichiro , Yamaguchi Takuhiro
Published: October 2012

Leafminer flies, especially, Liriomyza huidobrensis, Liriomyza sativae and Liriomyza trifolii, are quarantine species in many countries. Their morphological similarity makes identification difficult. To develop a rapid, reliable, sensitive and simple molecular identification method using multiplex PCR, we newly sequenced the mitochondrial cytochrome oxidase I (COI) genes of Liriomyza bryoniae, Liriomyza chinensis, L. huidobrensis, L. sativae, L. trifolii, Chromatomyia horticola and four parasitoid species. We aligned them with all the COI sequences of the leafminer flies found in the international DNA nucleotide sequence databases (DDBJ/EMBL/GenBank). We then designed species‐specific primers to allow us to differentiate between L. bryoniae, L. chinensis, L. huidobrensis, L. sativae, and L. trifolii.
Train the trainer? A randomized controlled trial of a multi‐tiered oral health education programme in community‐based residential services for adults with intellectual disability
Authors: Mac Giolla Phadraig Caoimhin , Guerin Suzanne , Nunn June
Published: October 2012

Objectives

To assess the impact of a multi‐tiered oral health education programme on care staff caring for people with intellectual disability (ID).

Methods

Postal questionnaires were sent to all care staff of a community‐based residential care service for adults, randomly assigned to control and intervention groups. A specifically developed training programme was delivered to residential staff nominees, who then trained all staff within the intervention group. The control group received no training. Post‐test questionnaires were sent to both groups. Paired‐samples t‐test was used to compare oral health‐related knowledge (K) and behaviour, attitude and self‐efficacy (BAS) scores.

Results

Of the initial 219 respondents, 154 (response rate between 40% and 35.8%, with attrition rate of 29.7% from baseline to repeat) returned completed questionnaires at post‐test (M = 8.5 months, range = 6.5–11 months). Control and intervention groups were comparable for general training, employment and demographic variables. In the intervention group, mean Knowledge Index score rose from K = 7.2 to K = 7.9 (P < 0.001) and mean BAS scale score rose from BAS = 4.7 to BAS = 5.4 (P < 0.001). There was no statistically significant increase in mean scores from test (K = 7.0, BAS = 4.7) to post‐test (K = 7.2, BAS = 4.9) for the control group.

Conclusions

Mean scores regarding knowledge, attitude, self‐efficacy and reported behaviour increased significantly at 8.5 months in staff where training was provided. The results indicate that a multi‐tiered training programme improved knowledge, attitude, self‐efficacy and reported behaviour amongst staff caring for people with ID.
Buccal bone plate remodeling after immediate implants with or without synthetic bone grafting and flapless surgery: a histomorphometric and fluorescence study in dogs
Authors: Suaid Flávia A. , Novaes Arthur B. , Queiroz Adriana C. , Muglia Valdir A. , Almeida Adriana L. G. , Grisi Márcio F. M.
Published: October 2012

Objective

The aim of this study was to evaluate the buccal bone plate remodeling after immediate implantation using the flapless approach with or without bone graft into the gap between the implant and the buccal bone.

Material and methods

Eight dogs had the mandibular bicuspids extracted without flaps, and four implants were installed on each side, totaling eight implants per animal. Randomly, in one side, the implants were positioned at the bone crest level (equicrestal), and on the opposite side, the implants were positioned 2 mm subcrestal. All the implants were positioned 2.0 mm from the buccal bone plate (gap) and associated or not with grafting material. Therefore, the following treatments were performed: implants subcrestal test (SCTG) with bone graft and control (SCCG) without bone graft, and equicrestal test (ECTG) with bone graft and control (ECCG) without bone graft. One week following the surgeries, metallic prostheses were installed. Bone markers were administered 1, 2, 4, and 12 weeks after implant placement for fluorescence analysis. Ground sections were prepared from 12‐week healing biopsies, and histomorphometry was performed.

Results

The histomorphometric evaluation presents significant better results for theECTGin the vertical crestal bone resorption, but the other parameters showed better results for theSCCG. The fluorescence evaluation in adjacent areas showed numerically different results between groups with a small decrease at 12 weeks, except for theSCCG, which was higher at this time. The distant area showed a continuous increase in the marked bone.

Conclusion

The equicrestally placed implants presented little or no loss of the buccal bone wall. The subcrestally positioned implants presented loss of buccal bone, regardless of the use of bone graft. However, the buccal bone was always coronal to the implant shoulder.Both the equicrestal and subcrestal groups were benefited in the early stages of bone healing as evidenced by the fluorescence analysis.
Performance of titanium alloy sintered porous‐surfaced (SPS) implants supporting mandibular overdentures during a 20‐year prospective study
Authors: Deporter Douglas , Pharoah Michael , Yeh Simon , Todescan Reynaldo , Atenafu Eshetu G.
Published: October 2012

Objective

This study was undertaken to assess short, sintered porous‐surfaced (SPS), press‐fit implants with mandibular overdentures to restore edentulous patients with severe mandibular resorption.

Materials and Methods

Implant lengths of 7, 8, 9, and 10 mm were used, all with 2‐mm polished collars, making the designed intrabony lengths 5, 6, 7, and 8 mm. Each patient received three non‐splinted implants placed using a two‐stage protocol.

Results

Only 22 (with 53 implants) of the original 52 patients were available after 20 years. All but one of these patients was functioning with their implant‐retained overdentures. Life table analysis accounted for all patients and implants, and showed a 20‐year survival of 73.4%. Analysis of carefully standardized radiographs revealed mean cumulative bone loss after 20 years of 0.67 mm relative to the polished collar‐SPSjunction.

Conclusions

ShortSPSimplants with mandibular overdentures can provide an acceptable treatment over a 20‐year period for fully edentulous patients with severe alveolar resorption.
Head‐to‐head comparison between Actigraph 7164 and GT1M accelerometers in adolescents
Authors: Tanha Tina , Tornberg Åsa B. , Wollmer Per , Dencker Magnus
Published: October 2012

We compared, head‐to‐head, the old generation Actigraph model 7164 with the new generation Actigraph GT1M accelerometer. A total of 15 randomly selected teenagers (eight girls and seven boys) were investigated. They performed a treadmill test wearing the two kinds of accelerometers around the waist simultaneously. The treadmill test consisted of three different levels of speed 4, 6 and 8 km h−1 for four consecutive minutes. Accelerometer counts per 1 sec epoch for the Actigraph GT1M versus the Actigraph 7164 were at 4 km h−1 21·6 ± 12·9 versus 26·5 ± 11·5 counts, at 6 km h−1 56·0 ± 23·2 versus 62·9 ± 25·6 counts and at 8 km h−1 142·6 ± 37·2 versus 156·4 ± 34·9 counts (P<0·01 for all levels of speed). Data from the old generation Actigraph 7164 and the new generation Actigraph GT1M accelerometers differ, where the Actigraph GT1M generates 10‐23% lower values. Correction equation for Actigraph GT1M was Actigraph 7164 = 5·2484 +  Actigraph GT1M counts × 1·0448. These results need to be taken into consideration when using these devices.
Impacts of past habitat loss and future climate change on the range dynamics of South African Proteaceae
Authors: Sarmento Cabral Juliano , Jeltsch Florian , Thuiller Wilfried , Higgins Steven , Midgley Guy F. , Rebelo Anthony G. , Rouget Mathieu , Schurr Frank M.
Published: October 2012

Aim

To assess how habitat loss and climate change interact in affecting the range dynamics of species and to quantify how predicted range dynamics depend on demographic properties of species and the severity of environmental change.

Location

South African Cape Floristic Region.

Methods

We use data‐driven demographic models to assess the impacts of past habitat loss and future climate change on range size, range filing and abundances of eight species of woody plants (Proteaceae). The species‐specific models employ a hybrid approach that simulates population dynamics and long‐distance dispersal on top of expected spatio‐temporal dynamics of suitable habitat.

Results

Climate change was mainly predicted to reduce range size and range filling (because of a combination of strong habitat shifts with low migration ability). In contrast, habitat loss mostly decreased mean local abundance. For most species and response measures, the combination of habitat loss and climate change had the most severe effect. Yet, this combined effect was mostly smaller than expected from adding or multiplying effects of the individual environmental drivers. This seems to be because climate change shifts suitable habitats to regions less affected by habitat loss. Interspecific variation in range size responses depended mostly on the severity of environmental change, whereas responses in range filling and local abundance depended mostly on demographic properties of species. While most surviving populations concentrated in areas that remain climatically suitable, refugia for multiple species were overestimated by simply overlying habitat models and ignoring demography.

Main conclusions

Demographic models of range dynamics can simultaneously predict the response of range size, abundance and range filling to multiple drivers of environmental change. Demographic knowledge is particularly needed to predict abundance responses and to identify areas that can serve as biodiversity refugia under climate change. These findings highlight the need for data‐driven, demographic assessments in conservation biogeography.
Systematic, large‐scale national biodiversity surveys: NeoMaps as a model for tropical regions
Authors: Ferrer‐Paris José R. , Rodríguez Jon P. , Good Tatjana C. , Sánchez‐Mercado Ada Y. , Rodríguez‐Clark Kathryn M. , Rodríguez Gustavo A. , Solís Angel
Published: October 2012

Aim

To test a method for rapidly and reliably collecting species distribution and abundance data over large tropical areas [known as Neotropical Biodiversity Mapping Initiative (NeoMaps)], explicitly seeking to improve cost‐ and time‐efficiencies over existing methods (i.e. museum collections, literature), while strengthening local capacity for data collection.

Location

Venezuela.

Methods

We placed a grid over Venezuela (0.5 × 0.5 degree cells) and applied a stratified sampling design to select a minimum set of 25 cells spanning environmental and biogeographical variation. We implemented standardized field sampling protocols for birds, butterflies and dung beetles, along transects on environmental gradients (‘gradsects’). We compared species richness estimates from our field surveys at national, bioregional and cell scales to those calculated from data compiled from museum collections and the literature. We estimated the variance in richness, composition, relative abundance and diversity between gradsects that could be explained by environmental and biogeographical variables. We also estimated total survey effort and cost.

Results

In one field season, we covered 8% of the country and recorded 66% of all known Venezuelan dung beetles, 52% of Pierid butterflies and 37% of birds. Environmental variables explained 27–60% of variation in richness for all groups and 13–43% of variation in abundance and diversity in dung beetles and birds. Bioregional and environmental variables explained 43–58% of the variation in the dissimilarity matrix between transects for all groups.

Main conclusions

NeoMaps provides reliable estimates of richness, composition and relative abundance, required for rigorous monitoring and spatial prediction. NeoMaps requires a substantial investment, but is highly efficient, achieving survey goals for each group with 1‐month fieldwork and about US$ 1–8 per km2. Future work should focus on other advantages of this type of survey, including the ability to monitor the changes in relative abundance and turnover in species composition, and thus overall diversity patterns.
Ferulsinaic acid attenuation of diabetic nephropathy
Authors: Sayed Ahmed A. R.
Published: October 2012

Eur J Clin Invest 2012

Background  Different factors are involved in the development of diabetic nephropathy (DN). Oxidative stress and inflammation play an important role in the pathogenesis of DN. Ferulsinaic Acid (FA) was isolated in 2007. In 2011, we found that FA prolonged the lifespan of C. elegans due to its antioxidative effect, and we hypothesized that FA restores the kidney function of diabetic rats via its antioxidant activity.

Methods  Male Wistar rats were injected with STZ and divided into 5 groups of 10 each: control, diabetic untreated, diabetic treated with 500, 750 and 1000 ng/kg FA. FA treatment was continued for 21 weeks after induction of diabetes.

Results  In the diabetic rats treated with FA, fasting blood sugar, HbA1C kidney/body weight ratio, creatinine, BUN, sodium and albuminurea were significantly decreased compared with untreated diabetic rats. Diabetic rats showed decreased activities of superoxide dismutase, glutathione peroxidase and catalase, increased concentrations of malondialdehyde and IL‐6 in the kidney homogenate. In addition levels of 8‐hydroxy‐2′‐deoxyguanosine in the urine and in the renal cortex DNA were increased. Moreover, severe destruction in glomerular and tubulointerstitial lesions such as glomerular sclerosis, atrophy, interstitial expansion and interstitial cellular infiltration was seen in the kidney of the diabetic untreated rats. Furthermore, the diabetic kidney was found to be positive for NF‐κB p65 antigen in the immunohistochemistry examinations. Treatment with FA restored all the altered parameters in a dose‐dependent manner. Furthermore, all the ultra‐morphologic abnormalities and NF‐κB activation in the kidney of diabetic rats were markedly ameliorated by FA treatment.

Conclusion  FA confers a considerable protection against kidney injuries of the diabetic rats by increasing activities of antioxidant enzymes, attenuating the formation of AGEs, attenuating the NF‐κB activation, ameliorating the inflammatory markers and inhibiting the accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.
Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain
Authors: Nokia Miriam S. , Anderson Megan L. , Shors Tracey J.
Published: October 2012

Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood–brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3–12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague–Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta‐band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the ‘chemobrain’.
Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety‐related behavior
Authors: Spencer Sade , Falcon Edgardo , Kumar Jaswinder , Krishnan Vaishnav , Mukherjee Shibani , Birnbaum Shari G. , McClung Colleen A.
Published: October 2012

It has been suggested for some time that circadian rhythm abnormalities underlie the development of multiple psychiatric disorders. However, it is unclear how disruptions in individual circadian genes might regulate mood and anxiety. Here we found that mice lacking functional mPeriod 1 (mPer1) or mPeriod 2 (mPer2) individually did not have consistent behavioral abnormalities in measures of anxiety‐related behavior. However, mice deficient in both mPer1 and mPer2 had an increase in levels of anxiety‐like behavior in multiple measures. Moreover, we found that mPer1 and mPer2 expression was reduced in the nucleus accumbens (NAc) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety‐related behavior. Following social defeat, chronic treatment with fluoxetine normalized Per gene expression towards wild‐type levels. Knockdown of both mPer1 and mPer2 expression via RNA interference specifically in the NAc led to a similar increase in anxiety‐like behavior as seen in the mutant animals. Taken together, these results implicate the Per genes in the NAc in response to stress and the development of anxiety.
A dimerization defect caused by a glycine substitution at position 420 by serine in tissue‐nonspecific alkaline phosphatase associated with perinatal hypophosphatasia
Authors: Makita Saori , Al‐Shawafi Hiba A. , Sultana Sara , Sohda Miwa , Nomura Shuichi , Oda Kimimitsu
Published: October 2012

Mutations in the tissue‐nonspecific alkaline phosphatase (TNSALP) gene cause hypophosphatasia (HPP), an inborn error of metabolism characterized by defects in bone and teeth mineralization accompanying subnormal levels of serum alkaline phosphatase activity. Missense mutations at position 420 of TNSALP (standard nomenclature), which convert glycine to serine [TNSALP (G420S)] or alanine [TNSALP (G420A)], have been reported in perinatal and childhood HPP, respectively. When expressed in COS‐1 cells, both TNSALP mutants were indistinguishable from wild‐type TNSALP [TNSALP (W)] as evidenced by immunofluorescence and western blotting. Nevertheless, the two TNSALP mutants did not show substantial alkaline phosphatase activity. In agreement with transiently transfected cells, TNSALP (G420S) expressed in a Tet‐On inducible expression system lacked its alkaline phosphatase activity, although this mutant was anchored to the cell surface lipid bilayers by glycosylphosphatidylinositol as an 80 kDa mature form bearing complex‐type oligosaccharides like TNSALP (W). Importantly, TNSALP (G420S) was found to largely fail to assemble into the homodimer in contrast to TNSALP (W). Taken together, these results demonstrate that the glycine residue at position 420 is crucial for the subunit interaction of TNSALP and hence its catalytic function without affecting trafficking of monomeric TNSALP. We conclude that the dimerization defect is the molecular basis for perinatal HPP associated with the genotype G420S/G420S.
CO2 fertilization and enhanced drought resistance in Greek firs from Cephalonia Island, Greece
Authors: Koutavas Athanasios
Published: October 2012

Growth–climate relationships were investigated in Greek firs from Ainos Mountain on the island of Cephalonia in western Greece, using dendrochronology. The goal was to test whether tree growth is sensitive to moisture stress, whether such sensitivity has been stable through time, and whether changes in growth–moisture relationships support an influence of atmospheric CO2 on growth. Regressions of tree‐ring indices (ad 1820–2007) with instrumental temperature, precipitation, and Palmer Drought Severity Index (PDSI) indicate that growth is fundamentally limited by growing‐season moisture in late spring/early summer, most critically during June. However, this simple picture obscures a pattern of sharply evolving growth–climate relationships during the 20th century. Correlations between growth and June temperature, precipitation, and PDSI were significantly greater in the early 20th century but later degraded and disappeared. By the late 20th–early 21st century, there remains no statistically significant relationship between moisture and growth implying markedly enhanced resistance to drought. Moreover, growth experienced a net increase over the last half‐century culminating with a sharp spike in ad 1988–1990. This recent growth acceleration is evident in the raw ring‐width data prior to standardization, ruling out artifacts from statistical detrending. The vanishing relationship with moisture and parallel enhancement of growth are all the more notable because they occurred against a climatic backdrop of increasing aridity. The results are most consistent with a significant CO2 fertilization effect operating through restricted stomatal conductance and improved water‐use efficiency. If this interpretation is correct, atmospheric CO2 is now overcompensating for growth declines anticipated from drier climate, suggesting its effect is unusually strong and likely to be detectable in other up‐to‐date tree‐ring chronologies from the Mediterranean.
HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity
Authors: Kogo Hiroshi , Tsutsumi Makiko , Inagaki Hidehito , Ohye Tamae , Kiyonari Hiroshi , Kurahashi Hiroki
Published: October 2012

Meiotic chromosome segregation requires homologous pairing, synapsis and crossover recombination during meiotic prophase. The checkpoint kinase ATR has been proposed to be involved in the quality surveillance of these processes, although the underlying mechanisms remain largely unknown. In our present study, we generated mice lacking HORMAD2, a protein that localizes to unsynapsed meiotic chromosomes. We show that this Hormad2 deficiency hampers the proper recruitment of ATR activity to unsynapsed chromosomes. Male Hormad2‐deficient mice are infertile due to spermatocyte loss as a result of characteristic impairment of sex body formation; an ATR‐ and γH2AX‐enriched repressive chromatin domain is formed, but is partially dissociated from the elongated sex chromosome axes. In contrast to males, Hormad2‐deficient females are fertile. However, our analysis of Hormad2/Spo11 double‐mutant females shows that the oocyte number is negatively correlated with the frequency of pseudo–sex body formation in a Hormad2 gene dosage‐dependent manner. This result suggests that the elimination of Spo11‐deficient asynaptic oocytes is associated with the HORMAD2‐dependent pseudo–sex body formation that is likely initiated by local concentration of ATR activity in the absence of double‐strand breaks. Our results thus show a HORMAD2‐dependent quality control mechanism that recognizes unsynapsis and recruits ATR activity during mammalian meiosis.
Use of Haemate® P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: a multicentre observational study
Authors: Rothschild C. , D'oiron R. , Borel‐derlon A. , Gruel Y. , Navarro R. , Negrier C.
Published: October 2012

Immune tolerance induction (ITI) can eliminate factor VIII (FVIII) inhibitory antibodies that appear during FVIII replacement therapy. If first‐line ITI fails, switching to a different FVIII concentrate, especially one containing von Willebrand factor (VWF), has been advocated. The objective of the study was to assess the efficacy and safety of Haemate® P, a plasma‐derived FVIII concentrate containing high levels of VWF, as ITI in severe haemophilia A patients who had failed at least one prior ITI attempt with a different FVIII concentrate. In this multicentre, observational study, Haemate® P was administered at a starting dose of 83–308 IU kg−1 day−1 (1500–6000 IU day−1). Efficacy was assessed by standard criteria (e.g. Bethesda titre, FVIII recovery and half‐life), and bleeding characteristics. Nine patients from six haemophilia centres were treated with Haemate® P after failing one (n = 2), two (n = 5) or three (n = 2) prior ITI courses. The median time from inhibitor detection to Haemate® P treatment was 5.4 years. The median Haemate® P dose was 134 IU kg−1, and the median treatment duration 32 months. During median of 47 months of follow‐up, complete response, partial response and treatment failure were observed in one, three and five patients respectively. Five patients experienced seven adverse events (AEs), including two serious AEs (sepsis). Haemate® P was discontinued due to an AE in one patient with a partial response. Haemate® P salvage ITI resulted in complete or partial tolerization in four of nine patients (44%) who had failed previous ITI attempts using different FVIII concentrates.
Haemophilia & Exercise Project (HEP): The impact of 1‐year sports therapy programme on physical performance in adult haemophilia patients
Authors: Czepa D. , von Mackensen S. , Hilberg T.
Published: October 2012

Episodes of bleeding in people with haemophilia (PWH) are associated with reduced activity and limitations in physical performance. Within the scope of the ‘Haemophilia & Exercise Project’ (HEP) PWH were trained in a sports therapy programme. Aim of this study was to investigate subjective and objective physical performance in HEP‐participants after 1 year training. Physical performance of 48 adult PWH was compared before and after sports therapy subjectively (HEP‐Test‐Q) and objectively regarding mobility (range of motion), strength and coordination (one‐leg‐stand) and endurance (12‐min walk test). Sports therapy included an independent home training that had previously been trained in several collective sports camps. Forty‐three controls without haemophilia and without training were compared to PWH. Of 48 PWH, 13 performed a regular training (active PWH); 12 HEP‐participants were constantly passive (passive PWH). Twenty‐three PWH and 24 controls dropped out because of incomplete data. The activity level increased by 100% in active PWH and remained constant in passive PWH, and in controls (P ≤ 0.05). Only mobility of the right knee was significantly improved in active PWH (+5.8 ± 5.3°) compared to passive PWH (−1.3 ± 8.6°). The 12‐min walk test proved a longer walking distance for active PWH (+217 ± 199 m) compared to controls (−32 ± 217 m). Active PWH reported a better subjective physical performance in the HEP‐Test‐Q domains ‘strength & coordination’, ‘endurance’ and in the total score (+9.4 ± 13.8) compared to passive PWH (−5.3 ± 13.5) and controls (+3.7 ± 7.5). The ‘mobility’‐scale and one‐leg‐stand remained unchanged. Sports therapy increases the activity level and physical performance of PWH, whereby objective effects do not always correspond with subjective assessments.
Interleukin‐15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab
Authors: Perrier Clémentine , Arijs Ingrid , Staelens Dominiek , Breynaert Christine , Cleynen Isabelle , Covens Kris , Ferrante Marc , Van Assche Gert , Vermeire Séverine , de Hertogh Gert , Schuit Frans , Rutgeerts Paul , Ceuppens Jan L.
Published: October 2012

Interleukin‐15 (IL‐15) is a pro‐inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL‐15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL‐15Rα). The aim of this study is to evaluate the expression of IL‐15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL‐15Rα, IL‐15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription‐PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL‐15Rα were measured in sera of patients by ELISA and IL‐15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL‐15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non‐responder patients. The concentration of sIL‐15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non‐responders either before or after IFX. CD patients have levels of sIL‐15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL‐15Rα+ cells closely resemble activated memory B cells with a pre‐plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL‐15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL‐15 regulates B‐cell functions during bowel inflammation. No change in release of sIL‐15Rα is observed in patients treated with IFX.
Genotypic characteristics of a Mycobacterium sp. isolated from yellowtail Seriola quinqueradiata and striped jack Pseudocaranx dentex in Japan
Authors: Imajoh Masayuki , Sugiura Hidehiro , Hashida Yumiko , Hatai Kishio , Oshima Syun‐ichirou , Daibata Masanori , Kawai Kenji
Published: October 2012

In Japan, a Mycobacterium marinum‐like mycobacterium was isolated from the yellowtail, Seriola quinqueradiata. The species was identified as M. marinum by a commercial mycobacterial DNA‐DNA hybridization kit. Nevertheless, PCR restriction analysis of the DNA of its RNA polymerase β‐subunit gene definitively showed that this Mycobacterium sp. was M. ulcerans. PCR analysis revealed the genotypic characteristics of M. ulcerans in the Mycobacterium sp., only the mup053 gene sequence being absent, as has been found previously in other piscine mycobacteria such as M. marinum strains DL240490 and DL045 and M. pseudoshottsii. With one exception, this Mycobacterium sp. and M. pseudoshottsii had identical 16S rRNA gene sequences, which is also probably true of M. marinum strains DL240490 and DL045. Similarly, according to comparisons of the 16S rRNA gene, ITS region, and hsp65 gene sequences, this Mycobacterium sp. is more closely related to M. pseudoshottsii than to M. ulcerans or M. marinum. A PCR product of approximately 2000 bp was amplified from region of difference 9 in the Mycobacterium sp. The nucleotide sequence revealed insertion of IS2404, the sequence of which is 1366 bp long. The novel single nucleotide polymorphisms identified in this region distinguished this Mycobacterium sp. from M. marinum strain DL240490 and M. pseudoshottsii. The present findings raise the possibility that these species have a common ancestor. Further studies are required to improve our understanding of the relationship between their geographical origin and genetic diversity.
Safety, tolerability and pharmacokinetics of a human anti‐interleukin‐13 monoclonal antibody (CNTO 5825) in an ascending single‐dose first‐in‐human study
Authors: van Hartingsveldt Bart , Nnane Ivo P. , Bouman‐Thio Esther , Loza Matthew J. , Piantone Alexa , Davis Hugh M. , Petty Kevin J.
Published: October 2012

Aims

To assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 5825 following single‐dose intravenous (i.v.) and subcutaneous (s.c.) administration in healthy and healthy atopic subjects.

Methods

Sixty‐four subjects received a single dose of placebo or CNTO 5825 (0.1, 0.3, 1.0, 3.0, or 10 mg kg−1 i.v. in a dose‐escalating manner, or 3.0 mg kg−1 s.c. in healthy subjects; and 10 mg kg−1 i.v. in healthy atopic subjects). Subjects were observed for 96 h postadministration and followed for 16 weeks. Safety and tolerability were monitored, and serum samples were collected to measure CNTO 5825 concentrations, antibodies to CNTO 5825 and PD biomarkers.

Results

Most adverse events were mild to moderate in severity and considered to be unrelated to CNTO 5825, with no dose‐dependent trends seen. The two serious adverse events were considered to be unrelated to CNTO 5825. After i.v. administration, CNTO 5825 exhibited linear PK, with a terminal half‐life of ∼22–32 days. After a single 3 mg kg−1 s.c. dose in healthy subjects, CNTO 5825 was absorbed into the systemic circulation with a median time to maximum serum concentration (tmax) of 5.45 days and absolute bioavailability of ∼75%. The PK profile of CNTO 5825 at 10 mg kg−1 was similar in both healthy and healthy atopic subjects. No antibodies to CNTO 5825 were detected through week 16. In the CNTO 5825‐treated healthy atopic subjects, there was a significant reduction in serum IgE and C‐C motif chemokine ligand 17 (P = 0.028 and 0.068 vs. placebo, respectively).

Conclusions

CNTO 5825 was well tolerated, had an acceptable safety profile, exhibited linear PK characteristics, and no detected antibodies to CNTO 5825.