bluuebunny/crossref_metadata_2025 huggingface dataset:
Seed Architecture Shapes Embryo Metabolism in Oilseed Rape
Authors: Borisjuk Ljudmilla , Neuberger Thomas , Schwender Jörg , Heinzel Nicolas , Sunderhaus Stephanie , Fuchs Johannes , Hay Jordan O. , Tschiersch Henning , Braun Hans-Peter , Denolf Peter , Lambert Bart , Jakob Peter M. , Rolletschek Hardy
Published: May 2013

Constrained to develop within the seed, the plant embryo must adapt its shape and size to fit the space available. Here, we demonstrate how this adjustment shapes metabolism of photosynthetic embryo. Noninvasive NMR-based imaging of the developing oilseed rape (Brassica napus) seed illustrates that, following embryo bending, gradients in lipid concentration became established. These were correlated with the local photosynthetic electron transport rate and the accumulation of storage products. Experimentally induced changes in embryo morphology and/or light supply altered these gradients and were accompanied by alterations in both proteome and metabolome. Tissue-specific metabolic models predicted that the outer cotyledon and hypocotyl/radicle generate the bulk of plastidic reductant/ATP via photosynthesis, while the inner cotyledon, being enclosed by the outer cotyledon, is forced to grow essentially heterotrophically. Under field-relevant high-light conditions, major contribution of the ribulose-1,5-bisphosphate carboxylase/oxygenase–bypass to seed storage metabolism is predicted for the outer cotyledon and the hypocotyl/radicle only. Differences between in vitro– versus in planta–grown embryos suggest that metabolic heterogeneity of embryo is not observable by in vitro approaches. We conclude that in vivo metabolic fluxes are locally regulated and connected to seed architecture, driving the embryo toward an efficient use of available light and space.
EXO70A1-Mediated Vesicle Trafficking Is Critical for Tracheary Element Development in Arabidopsis
Authors: Li Shipeng , Chen Min , Yu Dali , Ren Shichao , Sun Shufeng , Liu Linde , Ketelaar Tijs , Emons Anne-Mie C. , Liu Chun-Ming
Published: May 2013

Exocysts are highly conserved octameric complexes that play an essential role in the tethering of Golgi-derived vesicles to target membranes in eukaryotic organisms. Genes encoding the EXO70 subunit are highly duplicated in plants. Based on expression analyses, we proposed previously that individual EXO70 members may provide the exocyst with functional specificity to regulate cell type– or cargo-specific exocytosis, although direct evidence is not available. Here, we show that, as a gene expressed primarily during tracheary element (TE) development, EXO70A1 regulates vesicle trafficking in TE differentiation in Arabidopsis thaliana. Mutations of EXO70A1 led to aberrant xylem development, producing dwarfed and nearly sterile plants with very low fertility, reduced cell expansion, and decreased water potential and hydraulic transport. Grafting of a mutant shoot onto wild-type rootstock rescued most of these aboveground phenotypes, while grafting of a wild-type shoot to the mutant rootstock did not rescue the short root hair phenotype, consistent with the role of TEs in hydraulic transport from roots to shoots. Histological analyses revealed an altered pattern of secondary cell wall thickening and accumulation of large membrane-bound compartments specifically in developing TEs of the mutant. We thus propose that EXO70A1 functions in vesicle trafficking in TEs to regulate patterned secondary cell wall thickening.
Gerhard Henrik Armauer Hansen (1841–1912) – 100 years anniversary tribute
Authors: Grzybowski Andrzej , Kluxen Guido , Półtorak Klaudia
Published: May 2013

2012 marks the 100th year of death of Gerhard Henrik Armauer Hansen (1841–1912), who discovered Mycobacterium leprae, but also gave the first systematic scientific work on the leprosy of the eye. The article reviews his life and scientific achievements with special regard to eye and ophthalmology.
Pleistocene landscape entrenchment: a geomorphological mountain to foreland field case, the Las Tunas system, Argentina
Authors: Pepin E. , Carretier S. , Hérail G. , Regard V. , Charrier R. , Farías M. , García V. , Giambiagi L.
Published: May 2013

The study of the Las Tunas River incisions, located in the eastern Andean foreland front (3320’ S in Argentina), provides new clues for the interpretation of deep piedmont entrenchments. Both the Las Tunas mountain catchment and its piedmont are strongly entrenched with maximal incision of over 100 m at the mountain front. Three main terrace levels are well exposed and are labelled T1, T2 and T3 from the youngest to the oldest. We combined geological and geomorphological field observations, kinematic GPS data, satellite data and aerial photos with geochronological and analysis to provide a detailed description of terrace organization and a discussion of the evolution of the Las Tunas landscape. The surprisingly constant concentrations in surface layers as deep as 1.5 m show that gently dipping alluvial surfaces can be continuously and deeply mixed. Our data show a first period of deposition (Mesones Fm) before 0.85 Myr (minimum T3 age), followed by deep erosion and a second sedimentation period (Las Tunas Fm) that includes a ca. 0.6 Myr ash deposit. T2 and T1 are inset in the Las Tunas Fm and were abandoned ca. 15–20 kyr ago. The similar ages for T2 and T1 show that post‐20 kyr entrenchment occurred very rapidly. Despite Quaternary deformation in the Las Tunas piedmont, terrace entrenchment is best explained by paleo‐climatic changes. The terrace organization reveals that the erosion‐sedimentation phases affected the entire system from the piedmont toe to 10 km upstream of the mountain front. Finally, contrary to the neighbouring more deeply incised Diamante River system, where late Quaternary piedmont uplift is more likely to have been a factor causing incision, the more stable Las Tunas system provides an incomplete geomorphological record of Pleistocene and Holocene climate variations. We suggest that climate variations are better recorded in uplifting piedmonts than in stable ones, where the magnitude of incision and sedimentation and the fact that they occur repeatedly at the same elevation can erase a large part of the record.
Controls on fluvial sedimentary architecture and sediment‐fill state in salt‐walled mini‐basins: Triassic Moenkopi Formation, Salt Anticline Region, SE Utah, USA
Authors: Banham Steven G. , Mountney Nigel P.
Published: May 2013

The Triassic Moenkopi Formation in the Salt Anticline Region, SE Utah, represents the preserved record of a low‐relief ephemeral fluvial system that accumulated in a series of actively subsiding salt‐walled mini‐basins. Development and evolution of the fluvial system and its resultant preserved architecture was controlled by the following: (1) the inherited state of the basin geometry at the time of commencement of sedimentation; (2) the rate of sediment delivery to the developing basins; (3) the orientation of fluvial pathways relative to the salt walls that bounded the basins; (4) spatially and temporally variable rates and styles of mini‐basin subsidence and associated salt‐wall uplift; and (5) temporal changes in regional climate. Detailed outcrop‐based tectono‐stratigraphic analyses demonstrate how three coevally developing mini‐basins and their intervening salt walls evolved in response to progressive sediment loading of a succession of Pennsylvanian salt (the Paradox Formation) by the younger Moenkopi Formation, deposits of which record a dryland fluvial system in which flow was primarily directed parallel to a series of elongate salt walls. In some mini‐basins, fluvial channel elements are stacked vertically within and along the central basin axes, in response to preferential salt withdrawal and resulting subsidence. In other basins, rim synclines have developed adjacent to bounding salt walls and these served as loci for accumulation of stacked fluvial channel complexes. Neighbouring mini‐basins exhibit different styles of infill at equivalent stratigraphic levels: sand‐poor basins dominated by fine‐grained, sheet‐like sandstone fluvial elements, which are representative of nonchannelised flow processes, apparently developed synchronously with neighbouring sand‐prone basins dominated by major fluvial channel‐belts, demonstrating effective partitioning of sediment route‐ways by surface topography generated by uplifting salt walls. Reworked gypsum clasts present in parts of the stratigraphy demonstrate the subaerial exposure of some salt walls, and their partial erosion and reworking into the fill of adjoining mini‐basins during accumulation of the Moenkopi Formation. Complex spatial changes in preserved stratigraphic thickness of four members in the Moenkopi Formation, both within and between mini‐basins, demonstrates a complex relationship between the location and timing of subsidence and the infill of the generated accommodation by fluvial processes.
Blunted hypothalamic‐pituitary‐adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight
Authors: Kaseva Nina , Wehkalampi Karoliina , Pyhälä Riikka , Moltchanova Elena , Feldt Kimmo , Pesonen Anu‐Katriina , Heinonen Kati , Hovi Petteri , Järvenpää Anna‐Liisa , Andersson Sture , Eriksson Johan G. , Räikkönen Katri , Kajantie Eero
Published: May 2013

Background

Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term‐born peers. This could be mediated through altered hypothalamic‐pituitary‐adrenal axis (HPAA) response to stress.

Objective

To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term‐born controls.

Design and participants

We studied 54 unimpaired young adults, aged 19–27 years, born at VLBW and a comparison group of 40 adults born at term, group‐matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST).

Measurements

In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed‐effects model and multiple linear regression analyses.

Results

Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed‐effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8–40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education.

Conclusions

VLBW adults have lower HPAA responses to psychosocial stress than term‐born controls. This is accompanied by a lower insulin response.
Have early postoperative complications from laparoscopic rectal cancer surgery improved over the past 20 years?
Authors: Shearer R. , Gale M. , Aly O. E. , Aly E. H.
Published: May 2013

Aim

Laparoscopic rectal cancer surgery has been increasingly used since 1991 following the publication of the first case series. Since then, several studies have confirmed that laparoscopic surgery for rectal cancer is challenging with associated morbidity and mortality. The aim of this study was to determine if the rates of early postoperative complications in laparoscopic rectal cancer surgery have improved over the past 20 years.

Method

A literature search of the EMBASE and MEDLINE databases between August 1991 and August 2011 was conducted using the keywords laparoscopy, rectal cancer and postoperative complications. Data were analysed using linear regression ANOVA performed in gnumerics software.

Results

Ninety‐seven studies were included for analysis. Over the last 20 years there has been no significant change in the rate of any early postoperative complications (anastomotic leak, conversion, sexual, urinary or faecal dysfunction, wound infection, overall morbidity or mortality). However, in the last 3 years, the rate of positive resection margins has decreased significantly (P = 0.01).

Conclusion

There was no evidence of a statistically significant change in early postoperative complications until 3 years ago. This may reflect the inherent morbidity associated with rectal surgery regardless of the approach used, the limitations of the current laparoscopic instrumentation or the relatively long learning curve. With increasing experience, a repeat analysis in the near future following the publication of ongoing randomized clinical trials might show improved outcomes.
Dearterialization with mucopexy versus haemorrhoidectomy for grade III or IV haemorrhoids: short‐term results of a double‐blind randomized controlled trial
Authors: Denoya P. I. , Fakhoury M. , Chang K. , Fakhoury J. , Bergamaschi R.
Published: May 2013

Aim

There is scepticism regarding anatomical rationale and Doppler guidance for ligation of haemorrhoidal arteries. The null hypothesis of this randomized controlled trial (RCT) was that there is no difference in pain following dearterialization or haemorrhoidectomy for grade III/IV internal haemorrhoids in a minimum of three quadrants.

Method

This was a single‐centre, double‐blind RCT. Patients were allocated to dearterialization or haemorrhoidectomy. Included haemorrhoids were grade III, prolapsing but reducible; and grade IV, chronic non‐incarcerated. The primary end‐point was pain. Patients with external component, acute incarcerated grade IV or recurrent haemorrhoids were not included. The interventions were dearterialization (with Doppler guidance and mucopexy) or haemorrhoidectomy. The main outcome measure was the Brief Pain Inventory (BPI).

Results

Twenty dearterialization patients were comparable to 20 haemorrhoidectomy patients for age (P = 0.107), body mass index (P = 0.559), race (P = 0.437), American Society of Anesthesiology score (P = 0.569), comorbidities (P = 0.592), grade (P = 0.096), quadrants (P = 0.222), Fecal Incontinence Quality‐of‐Life Score (FIQOL; P = 0.388), coping (P = 0.532), depression (P = 0.505), embarrassment (P = 0.842), and Short Form Health Survey (SF‐12) physical components (P = 0.337), SF‐12 mental components (P = 0.396) and constipation (P = 0.628) scores. Dearterialization patients had shorter operative time (36 vs 54 min, P = 0.043) with less pain (P = 0.011) and urinary retention (P = 0.012). Dearterialization patients had first bowel movement earlier (1.3 vs 4.6 days, P = 0.001), less pain (P = 0.011) and lower pain intensity (P = 0.001). Narcotic requirements were reduced in dearterialization patients (25% vs 100%, P = 0.001), with less medication (4.9 vs 112 pills, P = 0.001) and shorter regimen (0 vs 7 days, P = 0.001). BPI did not differ on days 1, 3, 5, 7 and 14 except for less pain in dearterialization patients. At 3 months, symptomatic relief was the same with no differences in BPI, FIQOL or SF‐12.

Conclusion

Compared with haemorrhoidectomy, dearterialization led to less pain in grade III/IV haemorrhoids.
Clinical validity of tissue carcinoembryonic antigen expression as ancillary to serum carcinoembryonic antigen concentration in patients curatively resected for colorectal cancer
Authors: Park J. W. , Chang H. J. , Kim B. C. , Yeo H. Y. , Kim D. Y.
Published: May 2013

Aim

Although serum carcinoembryonic antigen (CEA) level is prognostic in colorectal cancer, the prognostic role of tumour CEA expression is unclear. The aim of this study is to identify the prognostic and surveillance roles of tissue CEA expression along with serum CEA concentration in patients curatively resected for colorectal cancer.

Method

Between January and December 2003, 294 patients who underwent curative resection for colorectal cancer were included in the study. Correlation of tissue CEA expression with overall survival (OS), disease‐free survival (DFS) and elevated serum CEA concentration at tumour recurrence were analysed.

Results

Tissue CEA expression was positive in 215 patients (73.1%). CEA expression was an independent prognostic factor for OS [hazard ratio (HR) = 2.537, 95% confidence interval (CI) = 1.065–6.042, P = 0.035] and DFS (HR = 3.090, 95% CI = 1.405–6.795, P = 0.005). Elevation of serum CEA at tumour recurrence was significantly lower in patients without than with tissue CEA expression (14.3 vs 57.6%, P = 0.045). Moreover, when patients were grouped according to a combination of serum CEA elevation and tissue CEA expression, those with tissue CEA expression and elevated serum CEA (group 3) had significantly poorer OS and DFS (P < 0.001 each) than those without CEA expression and elevated serum CEA (group 1) and those with either tissue CEA expression or elevated serum CEA (group 2). OS (P = 0.006) and DFS (P = 0.027) were both significantly greater in group 1 than in group 2.

Conclusion

Tissue CEA expression is a prognostic factor in patients with colorectal cancer. Analysis of tissue CEA expression may be helpful in determining the clinical utility of serial measurements of serum CEA as surveillance in patients with curatively resected colorectal cancer.
CT scan‐based modelling of anastomotic leak risk after colorectal surgery
Authors: Gervaz P. , Platon A. , Buchs N. C. , Rocher T. , Perneger T. , Poletti P.‐A.
Published: May 2013

Aim

Prolonged ileus, low‐grade fever and abdominal discomfort are common during the first week after colonic resection. Undiagnosed anastomotic leak carries a poor outcome and computed tomography (CT) scan is the best imaging tool for assessing postoperative abdominal complications. We used a CT scan‐based model to quantify the risk of anastomotic leak after colorectal surgery.

Method

A case–control analysis of 74 patients who underwent clinico‐radiological evaluation after colorectal surgery for suspicion of anastomotic leak was undertaken and a multivariable analysis of risk factors for leak was performed. A logistic regression model was used to identify determinant variables and construct a predictive score.

Results

Out of 74 patients with a clinical suspicion of anastomotic leak, 17 (23%) had this complication confirmed following repeat laparotomy. In multivariate analysis, three variables were associated with anastomotic leak: (1) white blood cells count > 9 × 109/l (OR = 14.8); (2) presence of ≥ 500 cm3 of intra‐ abdominal fluid (OR = 13.4); and (3) pneumoperitoneum at the site of anastomosis (OR = 9.9). Each of these three parameters contributed one point to the risk score. The observed risk of leak was 0, 6, 31 and 100%, respectively, for patients with scores of 0, 1, 2 and 3. The area under the receiver operating characteristic curve for the score was 0.83 (0.72–0.94).

Conclusion

This CT scan‐based model seems clinically promising for objective quantification of the risk of a leak after colorectal surgery.
Variation in colorectal cancer treatment and survival: a cohort study covering the East Anglia region
Authors: Warwick J. , Will O. , Allgood P. , Miller R. , Duffy S. , Greenberg D.
Published: May 2013

Aim

National guidelines for colorectal cancer management aim to optimize cancer outcomes irrespective of postcode. However, in order to ensure equal performance of cancer services, variation in outcome must be monitored and intelligently assessed. In this study, detailed regional cancer registry data were used to quantify and explore the reasons for variation in colorectal cancer outcomes at nine hospitals in East Anglia.

Method

We analysed data on colorectal cancers registered by the Eastern Cancer Registry and Information Centre (ECRIC) between 1999 and 2005. Tumours were grouped by site, in keeping with surgical resection. Multivariable Cox regression models were used to identify the effects of patient, disease and treatment variables on an individual's risk of death.

Results

After adjusting for demographic, disease and treatment variables there were significant differences in survival among hospitals in emergency admissions with cancer of the right colon, in elective admissions with cancer of the left, sigmoid or recto‐sigmoid colon and in emergency admissions with cancer of the rectum. There were also differences among hospitals in terms of perioperative death, nonsurgical management and numbers of nodes examined. For rectal cancers, rates of anterior resection compared with abdominoperineal excision differed, as well as the use of neoadjuvant radiotherapy.

Conclusion

Detailed analysis of demographic, disease and treatment factors are required when comparing the survival of individuals with colorectal cancer across hospitals. The results imply that cancer management was not consistent across East Anglia in 1999–2005 but the reasons for this are uncertain. Nevertheless, 5‐year age‐standardized survival with colon cancer in the Anglia Cancer Network region is currently among the best in the UK.
Evolution of intravascular assessment of coronary anatomy and physiology: from ultrasound imaging to optical and flow assessment
Authors: Sanidas Elias , Dangas George
Published: May 2013

The fact that coronary angiography has limitations in terms of precise estimation and progression of atherosclerosis has been partially overcome during the last years by the use of new techniques. Catheter‐based invasive modalities are of a profound clinical importance in regard to accurate assessment of coronary anatomy and physiology and the choice of the appropriate treatment strategy for each patient. Also their potential in clinical investigation projects is of great interest. This current review summarizes the basic principles of these methodologies and evidently highlights not only their use in clinical practice but also their contribution in clinical outcomes.
Identification, comparison, and functional analysis of salivary phenol‐oxidizing enzymes in Bemisia tabaci B and Trialeurodes vaporariorum
Authors: Peng Lu , Yan Ying , Yang Chun Hong , De Barro Paul J. , Wan Fang Hao
Published: May 2013

The differences in the ability of the invading whitefly, Bemisia tabaci (Gennadius) (commonly known as biotype B and hereafter as B) and Trialeurodes vaporariorum (Westwood) (both Hemiptera: Aleyrodidae) to utilize salivary phenol‐oxidizing enzymes – polyphenol oxidase (PPO) and peroxidase (POD) to detoxify plant defensive phenolic compounds were explored. Polyphenol oxidase and POD were found in the saliva of both B and T. vaporariorum. For tomato colonies, the PPO and POD activities in the watery saliva of B were 2.27‐ and 1.34‐fold higher than those of T. vaporariorum. The PPO activities against specific phenolic compounds commonly found in plants were compared. The activities of those from B were significantly greater than those from T. vaporariorum. We also measured PPO activity in both species after they had fed on plants that were undamaged or had been previously damaged with either a plant pathogen [Phytophthora infestans (Mont.) de Bary (Peronosporales)] infection, mechanical damage, B infestation, or exogenous salicylic acid. For B, PPO activities in watery saliva increased 229, 184, 152, and 139% in response to the four treatments, whereas those of T. vaporariorum only increased 133, 119, 113, and 103%, respectively. Biotype B infestation significantly increased the total phenolic content of tomato leaves. Meanwhile, feeding on tomato infestation with B had no significant effect on the survival rate of B, but decreased the survival rate of T. vaporariorum significantly. These results suggest that B has stronger ability utilizing PPO to detoxify high concentrations of phenolics than T. vaporariorum, and this contributes to a significant advantage for B to hold high fitness on plants with induced resistance. Possible roles of salivary PPO in the competition between B and T. vaporariorum are discussed.
Performance and prospects of Rag genes for management of soybean aphid
Authors: Hesler Louis S. , Chiozza Mariana V. , O'Neal Matthew E. , MacIntosh Gustavo C. , Tilmon Kelley J. , Chandrasena Desmi I. , Tinsley Nicholas A. , Cianzio Silvia R. , Costamagna Alejandro C. , Cullen Eileen M. , DiFonzo Christina D. , Potter Bruce D. , Ragsdale David W. , Steffey Kevin , Koehler Kenneth J.
Published: May 2013

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is an invasive insect pest of soybean [Glycine max (L.) Merr. (Fabaceae)] in North America, and it has led to extensive insecticide use in northern soybean‐growing regions there. Host plant resistance is one potential alternative strategy for managing soybean aphid. Several Rag genes that show antibiosis and antixenosis to soybean aphid have been recently identified in soybean, and field‐testing and commercial release of resistant soybean lines have followed. In this article, we review results of field tests with soybean lines containing Rag genes in North America, then present results from a coordinated regional test across several field sites in the north‐central USA, and finally discuss prospects for use of Rag genes to manage soybean aphids. Field tests conducted independently at multiple sites showed that soybean aphid populations peaked in late summer on lines with Rag1 or Rag2 and reached economically injurious levels on susceptible lines, whereas lines with a pyramid of Rag1 + Rag2 held soybean aphid populations below economic levels. In the regional test, aphid populations were generally suppressed by lines containing one of the Rag genes. Aphids reached putative economic levels on Rag1 lines for some site years, but yield loss was moderated, indicating that Rag1 may confer tolerance to soybean aphid in addition to antibiosis and antixenosis. Moreover, no yield penalty has been found for lines with Rag1, Rag2, or pyramids. Results suggest that use of aphid‐resistant soybean lines with Rag genes may be viable for managing soybean aphids. However, virulent biotypes of soybean aphid were identified before release of aphid‐resistant soybean, and thus a strategy for optimal deployment of aphid‐resistant soybean is needed to ensure sustainability of this technology.
Human Drg1 is a potassium‐dependent GTPase enhanced by Lerepo4
Authors: Pérez‐Arellano Isabel , Spínola‐Amilibia Mercedes , Bravo Jerónimo
Published: May 2013

Human Drg1, a guanine nucleotide binding protein conserved in archaea and eukaryotes, is regulated by Lerepo4. Together they form a complex which interacts with translating ribosomes. Here we have purified and characterized the GTPase activity of Drg1 and three variants, a shortened mutant depleted of the TGS domain, a phosphomimicking mutant and a construct with the two combined mutations. Our data reveal that potassium strongly stimulates the GTPase activity, without changing the monomeric status of Drg1 and that this activity is notably reduced in the mutants. The nature of Lerepo4 association has also been investigated. Dissecting the role of the different domains revealed that Dfrp domain is the sole responsible for the Drg1 increase in thermal stability and the four fold stimulation over its catalytic activity. Lerepo4 action leaves Drg1 affinity for nucleotides unaffected, feasibly favoring a switch I reorientation, mainly via the TGS domain. Drg1 displayed a high temperature optimum of activity at 42°C, suggesting the ability of being active under possible heat stress conditions.

Structured digital abstract

Drg1 and Drg1 bind by molecular sieving (View Interaction: 1, 2)
Strong genetic influences on measures of behavioral‐regulation among inbred rat strains
Authors: Richards J. B. , Lloyd D. R. , Kuehlewind B. , Militello L. , Paredez M. , Solberg Woods L. , Palmer A. A.
Published: May 2013

A fundamental challenge for any complex nervous system is to regulate behavior in response to environmental challenges. Three measures of behavioral‐regulation were tested in a panel of eight inbred rat strains. These measures were: (1) sensation seeking as assessed by locomotor response to novelty and the sensory reinforcing effects of light onset, (2) attention and impulsivity, as measured by a choice reaction time task and (3) impulsivity as measured by a delay discounting task. Deficient behavioral‐regulation has been linked to a number of psychopathologies, including ADHD, Schizophrenia, Autism, drug abuse and eating disorders. Eight inbred rat strains (August Copenhagen Irish, Brown Norway, Buffalo, Fischer 344, Wistar Kyoto, Spontaneous Hypertensive Rat, Lewis, Dahl Salt Sensitive) were tested. With n = 9 for each strain, we observed robust strain differences for all tasks; heritability was estimated between 0.43 and 0.66. Performance of the eight inbred rat strains on the choice reaction time task was compared to the performance of outbred Sprague Dawley (n = 28) and Heterogeneous strain rats (n = 48). The results indicate a strong genetic influence on complex tasks related to behavioral‐regulation and indicate that some of the measures tap common genetically driven processes. Furthermore, our results establish the potential for future studies aimed at identifying specific alleles that influence variability for these traits. Identification of such alleles could contribute to our understanding of the molecular genetic basis of behavioral‐regulation, which is of fundamental importance and likely contributes to multiple psychiatric disorders.
Rapamycin unbalances the polarization of human macrophages to M1
Authors: Mercalli Alessia , Calavita Ines , Dugnani Erica , Citro Antonio , Cantarelli Elisa , Nano Rita , Melzi Raffaella , Maffi Paola , Secchi Antonio , Sordi Valeria , Piemonti Lorenzo
Published: May 2013

Plasticity is a hallmark of macrophages, and in response to environmental signals these cells undergo different forms of polarized activation, the extremes of which are called classic (M1) and alternative (M2). Rapamycin (RAPA) is crucial for survival and functions of myeloid phagocytes, but its effects on macrophage polarization are not yet studied. To address this issue, human macrophages obtained from six normal blood donors were polarized to M1 or M2 in vitro by lipopolysaccharide plus interferon‐γ or interleukin‐4 (IL‐4), respectively. The presence of RAPA (10 ng/ml) induced macrophage apoptosis in M2 but not in M1. Beyond the impact on survival in M2, RAPA reduced CXCR4, CD206 and CD209 expression and stem cell growth factor‐β, CCL18 and CCL13 release. In contrast, in M1 RAPA increased CD86 and CCR7 expression and IL‐6, tumour necrosis factor‐α and IL‐1β release but reduced CD206 and CD209 expression and IL‐10, vascular endothelial growth factor and CCL18 release. In view of the in vitro data, we examined the in vivo effect of RAPA monotherapy (0·1 mg/kg/day) in 12 patients who were treated for at least 1 month before islet transplant. Cytokine release by Toll‐like receptor 4‐stimulated peripheral blood mononuclear cells showed a clear shift to an M1‐like profile. Moreover, macrophage polarization 21 days after treatment showed a significant quantitative shift to M1. These results suggest a role of mammalian target of rapamycin (mTOR) into the molecular mechanisms of macrophage polarization and propose new therapeutic strategies for human M2‐related diseases through mTOR inhibitor treatment.
Zirconium Incorporation into CaTiO3 Perovskite Prepared from Xerogels and Implication for the Fate of (Ca,Sr)TiO3 Nuclear Waste Ceramics
Authors: Navi Nissim U. , Kimmel Giora , Yardeni Guy , Zabicky Jacob , Shneck Roni Z. , Mintz Moshe H. , Navrotsky Alexandra
Published: May 2013

CaTiO3 perovskite has been proposed as a ceramic waste form for immobilization of 90Sr. Nonradioactive coprecipitated xerogel powders with nominal atomic ratios of Ca:Zr:Ti = 0.75:0.25:1.00 were synthesized to mimic the fate of (Ca0.7590Sr0.25)TiO3 solid solution after complete decay of the Sr and its intermediate product Y to stable Zr when an excess B4+ (Ti and 90Zr) cations will present. Ca:Ti = 1.00:1.00 samples were used as a reference. The powders were heated to various conditions to explore the thermodynamic stability of its oxides. The heated Ca:Zr:Ti = 0.75:0.25:1.00 samples formed a major orthorhombic Ca(Zr1−xTix)O3 perovskite phase. The Ti/(Ti + Zr) ratio of the perovskite preserves its nominal ratio at 600°C. The Zr rejects from the Ca(Zr1−xTix)O3 with further increasing the temperature, following the formation of Ca–Ti–Zr–O secondary phases. This study indicates a tendency of the Zr to segregate from an original (Ca,Sr)TiO3 waste form when the stoichiometry is controlled by the conversion of Sr to Zr (in normal oxidation states).
Material Evidence for Multiple Firings of Ancient Athenian Red‐Figure Pottery
Authors: Walton Marc , Trentelman Karen , Cummings Marvin , Poretti Giulia , Maish Jeff , Saunders David , Foran Brendan , Brodie Miles , Mehta Apurva
Published: May 2013

The production of Athenian fine ware pottery, produced between the 6th and 4th centuries B.C., required alternating the high‐temperature kiln between oxidative and reductive environments during a single firing to create the iconic red and black decorative scenes. Here, we show that the production of this pottery was even more complex, with vessels subjected to two, or possibly more, firings in the kiln, with applications of slip between each firing. On a representative sherd, we compared three painted black decorative features—relief line, contour line, and background slip. Scanning transmission electron microscopy (STEM) of the slips revealed that the relief line had a more melted microstructure than either the contour line or background slip. By characterizing the chemistry and micromorphology of the slips, we find that the relief line microstructure could only be produced through a separate firing, at a hotter temperature, than the other two decorative features.
Enhanced Thermoelectric Properties in Cu‐Doped c‐Axis‐Oriented Ca3Co4O9+δ Thin Films
Authors: Wei Renhuai , Jian Hongbin , Tang Xianwu , Yang Jie , Hu Ling , Chen Li , Dai Jianming , Zhu Xuebin , Sun Yuping
Published: May 2013

Highly c‐axis‐oriented Ca3Co4−xCuxO9+δ (x = 0, 0.1, 0.2, and 0.3) thin films were prepared by chemical solution deposition on LaAlO3 (001) single‐crystal substrates. X‐ray diffraction, field‐emission scanning electronic microscopy, X‐ray photoelectron spectroscopy, and ultraviolet‐visible absorption spectrums were used to characterize the derived thin films. The solubility limit of Cu was found to be less than 0.2, above which [Ca2(Co0.65Cu0.35)2O4]0.624CoO2 with quadruplicated rock‐salt layers was observed. The electrical resistivity decreased monotonously with increasing Cu‐doping content when x ≤ 0.2, and then slightly increased with further Cu doping. The Seebeck coefficient was enhanced from ~100 μV/K for the undoped thin film to ~120 μV/K for the Cu‐doped thin films. The power factor was enhanced for about two times at room temperature by Cu doping, suggesting that Cu‐doped Ca3Co4O9+δ thin films could be a promising candidate for thermoelectric applications.
Experimental evidence for trait utility of gill raker number in adaptive radiation of a north temperate fish
Authors: Roesch C. , Lundsgaard‐Hansen B. , Vonlanthen P. , Taverna A. , Seehausen O.
Published: May 2013

North temperate fish in post‐glacial lakes are textbook examples for rapid parallel adaptive radiation into multiple trophic specialists within individual lakes. Speciation repeatedly proceeded along the benthic–limnetic habitat axis, and benthic–limnetic sister species diverge in the number of gill rakers. Yet, the utility of different numbers of gill rakers for consuming benthic vs. limnetic food has only very rarely been experimentally demonstrated. We bred and raised families of a benthic–limnetic species pair of whitefish under common garden conditions to test whether these species (i) show heritable differentiation in feeding efficiency on zooplankton, and (ii) whether variation in feeding efficiency is predicted by variation in gill raker numbers. We used zooplankton of three different size classes to investigate prey size dependency of divergence in feeding efficiency and to investigate the effect strength of variation in the number of gill rakers. Our results show strong interspecific differences in feeding efficiency. These differences are largest when fish were tested with the smallest zooplankton. Importantly, feeding efficiency is significantly positively correlated with the number of gill rakers when using small zooplankton, also when species identity is statistically controlled for. Our results support the hypothesis that a larger number of gill rakers are of adaptive significance for feeding on zooplankton and provide one of the first experimental demonstrations of trait utility of gill raker number when fish feed on zooplankton. These results are consistent with the suggested importance of divergent selection driven feeding adaptation during adaptive radiation of fish in post‐glacial lakes.
The influence of gluten on clinical and immunological status of common marmosets (Callithrix jacchus)
Authors: Kuehnel Friederike , Mietsch Matthias , Buettner Thomas , Vervuert Ingrid , Ababneh Rayan , Einspanier Almuth
Published: May 2013

Background

Common marmosets (Callithrix jacchus) are susceptible to gastrointestinal diseases. Sensitivity to nutritional elements, for example gluten, has been suggested, but a serological screening has not been performed yet.

Methods

A gluten‐containing diet was offered to 24 animals, followed by a gluten‐free diet. During these diets, serum IgA antibodies to gliadin (AGA), tissue transglutaminase (tTG), deamidated gliadin (ADGA), and glycoprotein 2 (AGP2A) were determined. Body weight, diarrhea, and other clinical symptoms were recorded.

Results

Gluten increased AGA, tTG, and AGP2A concentrations in 13 of 24 animals. A significant decline of AGA and AGP2A was seen on gluten withdrawal. Positive (AGA, tTG) animals presented diarrhea more frequently on gluten‐containing diet and showed significantly increased body weight on gluten‐free diet compared to negative animals.

Conclusion

Gluten ingestion caused gastrointestinal symptoms in common marmosets, which disappeared on gluten withdrawal. Considering the immunological response to both diets, gluten sensitivity seems to be most likely.
Neuroprotective effects of donepezil against Aβ42‐induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK‐3β and nAChRs activity
Authors: Noh Min‐Young , Koh Seong H. , Kim Sung‐Min , Maurice Tangui , Ku Sae‐Kwang , Kim Seung H.
Published: May 2013

The main purpose of this study was to evaluate whether donepezil, acetylcholinesterase inhibitor, shown to play a protective role through inhibiting glycogen synthesis kinase‐3β (GSK‐3β) activity, could also exert neuroprotective effects by stimulating protein phosphatase 2A (PP2A) activity in the amyloid‐beta (Aβ)42‐induced neuronal toxicity model of Alzheimer's disease. In Aβ42‐induced toxic conditions, each PP2A and GSK‐3β activity measured at different times showed time‐dependent reverse pattern toward the direction of accelerating neuronal deaths with the passage of time. In addition, donepezil pre‐treatment showed dose‐dependent stepwise increase of neuronal viability and stimulation of PP2A activity. However, such effects on them were significantly reduced through the depletion of PP2A activity with either okadaic acid or PP2Ac siRNA. In spite of blocked PP2A activity in this Aβ42 insult, however, donepezil pretreatment showed additional significant recovering effect on neuronal viability when compared to the value without donepezil. Moreover, donepezil partially recovered its dephosphorylating effect on hyperphosphorylated tau induced by Aβ42. This observation led us to assume that additional mechanisms of donepezil, including its inhibitory effect on GSK‐3β activity and/or the activation role of nicotinic acetylcholine receptors (nAChRs), might be involved. Taken together, our results suggest that the neuroprotective effects of donepezil against Aβ42‐induced neurotoxicity are mediated through activation of PP2A, but its additional mechanisms including regulation of GSK‐3β and nAChRs activity would partially contribute to its effects.

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We investigated neuroprotective mechanisms of donepezil against Aβ42 toxicity: Donepezil increased neuronal viability with reduced p‐tau by enhancing PP2A activity. Despite of blocked PP2A activity, donepezil showed additional recovering effect on neuronal viability, which findings led us to assume that additional mechanisms of donepezil including its inhibitory effect on GSK‐3β activity and activating role of nicotinic AChRs might be involved.
NativeSTIM2 andORAI1 proteins form a calcium‐sensitive and thapsigargin‐insensitive complex in cortical neurons
Authors: Gruszczynska‐Biegala Joanna , Kuznicki Jacek
Published: May 2013

In non‐excitatory cells, stromal interaction molecule 1 (STIM1) andSTIM2 mediate store‐operated calcium entryviaan interaction withORAI1 calcium channels. However, in neurons,STIM2 over‐expression appears to play a role in calcium homeostasis that is different fromSTIM1 over‐expression. The aim of this study was to establish the role and localization of nativeSTIM2 in the neuronal cell. Co‐immunoprecipitation experiments revealed that the interaction between endogenousSTIM2 andORAI1 was greater in a low‐calcium medium than in a high‐calcium medium. Using a Proximity Ligation Assay (PLA), the number of apparent complexes of endogenousSTIM2 withORAI1 was quantified. No change in the number ofPLAsignals was observed in the presence of thapsigargin, which depletes calcium from the endoplasmic reticulum (ER). However, the number of apparentSTIM2‐ORAI1 complexes increased when intracellular and subsequentlyERcalcium concentrations were decreased byBAPTA‐AMor a low‐calcium medium. Both Fura‐2 acetoxymethyl ester calcium imaging andPLAin the same neuronal cell indicated that the calcium responses correlated strongly with the number of endogenousSTIM2‐ORAI1 complexes. The small drop in calcium levels in theERcaused by decreased intracellular calcium levels appeared to initiate the calcium‐sensitive and thapsigargin‐insensitive interaction betweenSTIM2 andORAI1.

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We show in neuronal somata the formation of endogenous complexes of stromal interaction molecule 2 (STIM2) with ORAI1 calcium channels. Their number increased when intracellular Ca2+concentrations were decreased by the Ca2+chelator BAPTA‐AM or a low‐calcium medium (EGTA), but did not in the presence of thapsigargin (TG). We conclude that the small drop of Ca2+level in endoplasmic reticulum, due to the decreased level of intracellular Ca2+, is sufficient to trigger STIM2‐ORAI1 complex formation in a thapsigargin‐insensitive manner.
Northern Adriatic phytoplankton response to short Po River discharge pulses during summer stratified conditions
Authors: Vilicic Damir , Kuzmic Milivoj , Tomažić Igor , Ljubešić Zrinka , Bosak Sunčica , Precali Robert , Djakovac Tamara , Marić Danijela , Godrijan Jelena
Published: May 2013

A 275‐km‐long transversel Northern Adriatic profile from the mouth of the Po River (Italian Adriatic coast) to the Kvarner region (Croatian coastal island area) was investigated in three successive case studies in August 2008, 2009 and 2010. The short Po River pulses in August result in the surface advection of riverine water, nutrients and phytoplankton from the western to the eastern side of the Adriatic. This surface spreading exhibits inter‐annual variability depending on the riverine discharge in the preceding period. The Po River discharge pulse in August 2010 in particular resulted in an extraordinary tongue‐like advection of riverine water, nutrients, and phytoplankton towards the Eastern Adriatic coast. The phenomenon was detected using both satellite imagery and classical oceanographic measurements. In the advective water, toxic dinoflagellates were most abundant in August 2010, when the influence of the Po was greatest.
Divergent evolutionary histories of two sympatric spruce bark beetle species
Authors: Bertheau Coralie , Schuler Hannes , Arthofer Wolfgang , Avtzis Dimitrios N. , Mayer François , Krumböck Susanne , Moodley Yoshan , Stauffer Christian
Published: May 2013

Ips typographus and Pityogenes chalcographus are two sympatric Palearctic bark beetle species with wide distribution ranges. As both species are comparable in biology, life history, and habitat, including sharing the same host, Picea abies, they provide excellent models for applying a comparative approach in which to identify common historical patterns of population differentiation and the influence of species‐specific ecological characteristics. We analysed patterns of genetic diversity, genetic structure and demographic history of ten I. typographus and P. chalcographus populations co‐distributed across Europe using both COI and ITS2 markers. Rather than similarities, our results revealed striking differences. Ips typographus was characterised by low genetic diversity, shallow population structure and strong evidence that all extant haplogroups arose via a single Holocene population expansion event. In contrast, genetic variation and structuring were high in P. chalcographus indicating a longer and more complex evolutionary history. This was estimated to be five times older than I. typographus, beginning during the last Pleistocene glacial maximum over 100 000 years ago. Although the expansions of P. chalcographus haplogroups also date to the Holocene or just prior to its onset, we show that these occurred from at least three geographically separated glacial refugia. Overall, these results suggest that the much longer evolutionary history of P. chalcographus greatly influenced the levels of phylogeographic subdivision among lineages and may have led to the evolution of different life‐history traits which in turn have affected genetic structure and resulted in an advantage over the more aggressive I. typographus.
Extreme genetic mixing within colonies of the wood‐dwelling termiteKalotermes flavicollis(Isoptera,Kalotermitidae)
Authors: Luchetti A. , Dedeine F. , Velonà A. , Mantovani B.
Published: May 2013

The existence of altruism in social insects is commonly attributed to altruistic individuals gaining indirect fitness through kin selection. However, recent studies suggest that such individuals might also gain direct fitness through reproduction. Experimental studies on primitive wood‐dwelling termites revealed that colony fusion often causes the death of primary reproductives (queen and king), allowing opportunities for workers to inherit the nest by developing into replacement reproductives (neotenics). Therefore, colony fusion has been proposed as an important factor that may have favoured sociality in termites. However, whether colony fusion occurs frequently in natural populations of wood‐dwelling termites remains an open question. We analysed eleven colonies of the wood‐dwelling termiteKalotermes flavicollis(Kalotermitidae), using two mitochondrial and five nuclear microsatellite markers. Nine of eleven colonies (82%) were mixed families, with offspring of three or more primary reproductives. To our knowledge, this result represents the highest frequency of mixed‐family colonies ever reported in termites. Moreover, genetic mixing of colonies appeared extreme in two ways. First, the number of haplotypes per colony was exceptionally high (up to nine), indicating that colonies were composed of multiple queens' offspring. Second, some mixed‐family colonies included individuals belonging to two highly divergent genetic lineages.F‐statistics and relatedness values suggest that mixed‐family colonies most likely result from colony fusion, giving support to the accelerated nest inheritance theory. These findings raise important questions about the mode of foundation of mixed‐family colonies and the evolutionary forces that maintain them within populations.