bluuebunny/crossref_metadata_2025 huggingface dataset:
Staged Hybrid Treatment for Contained Rupture of a Large Right Coronary Artery Aneurysm
Authors: Khoshbin Espeed , Sogliani Franco , Tang Augustine
Published: January 2014

We describe a staged approach to the management of a rare acute condition—contained rupture of a large right coronary artery aneurysm. A covered stent was deployed percutaneously to isolate the aneurysm at presentation followed by planned coronary bypass grafting. Treatment interval was complicated by new-onset pulmonary tuberculosis and subacute thrombosis of the covered stent leading to nonfatal inferior myocardial infarction. Coronary surgery was performed after complete antitubercular treatment and resolution of the acute pericarditis/thrombosis as a consequence of the contained rupture. The advantages of this staged approach included the following: (a) The covered stent prevented both acute myocardial infarction and progressive pseudoaneurysm expansion in the acute phase. (b) Deferred surgery was rendered technically less hazardous while avoiding the undesirable option of having to exclude an extremely calcified dominant right coronary artery. The patient made an excellent postoperative recovery with complete resolution of her symptoms at 6 weeks’ follow-up.
XenopusCdc7 executes its essential function early in S phase and is counteracted by checkpoint-regulated protein phosphatase 1
Authors: Poh Wei Theng , Chadha Gaganmeet Singh , Gillespie Peter J. , Kaldis Philipp , Blow J. Julian
Published: January 2014

The initiation of DNA replication requires two protein kinases: cyclin-dependent kinase (Cdk) and Cdc7. Although S phase Cdk activity has been intensively studied, relatively little is known about how Cdc7 regulates progression through S phase. We have used a Cdc7 inhibitor, PHA-767491, to dissect the role of Cdc7 inXenopusegg extracts. We show that hyperphosphorylation of mini-chromosome maintenance (MCM) proteins by Cdc7 is required for the initiation, but not for the elongation, of replication forks. Unlike Cdks, we demonstrate that Cdc7 executes its essential functions by phosphorylating MCM proteins at virtually all replication origins early in S phase and is not limiting for progression through theXenopusreplication timing programme. We demonstrate that protein phosphatase 1 (PP1) is recruited to chromatin and rapidly reverses Cdc7-mediated MCM hyperphosphorylation. Checkpoint kinases induced by DNA damage or replication inhibition promote the association of PP1 with chromatin and increase the rate of MCM dephosphorylation, thereby counteracting the previously completed Cdc7 functions and inhibiting replication initiation. This novel mechanism for regulating Cdc7 function provides an explanation for previous contradictory results concerning the control of Cdc7 by checkpoint kinases and has implications for the use of Cdc7 inhibitors as anti-cancer agents.
A conserved role for Snail as a potentiator of active transcription
Authors: Rembold Martina , Ciglar Lucia , Yáñez-Cuna J. Omar , Zinzen Robert P. , Girardot Charles , Jain Ankit , Welte Michael A. , Stark Alexander , Leptin Maria , Furlong Eileen E.M.
Published: January 2014

The transcription factors of the Snail family are key regulators of epithelial–mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ∼25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of “Snail-activated” genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development.
The diversity of receptor recognition in cholesterol‐dependent cytolysins
Authors: Tabata Atsushi , Ohkura Kazuto , Ohkubo Yukimasa , Tomoyasu Toshifumi , Ohkuni Hisashi , Whiley Robert A. , Nagamune Hideaki
Published: January 2014

Cholesterol‐dependent cytolysins (CDCs) are bacterial pore‐forming toxins secreted mainly by pathogenic Gram‐positive bacteria. CDCs generally recognize and bind to membrane cholesterol to create pores and lyse target cells. However, in contrast to typical CDCs such as streptolysin O, several atypical CDCs have been reported. The first of these was intermedilysin, which is secreted by Streptococcus intermedius and has human cell‐specificity, human CD59 (huCD59) being its receptor. In the study reported here, the diversity of receptor recognition among CDCs was investigated and multi‐receptor recognition characteristics were identified within this toxin family. Streptococcus mitis‐derived human platelet aggregation factor (Sm‐hPAF) secreted by S. mitis strain Nm‐65 isolated from a patient with Kawasaki disease was previously shown to hemolyze erythrocytes in a species‐dependent manner, its maximum activity being in human cells. In the present study, it was found that Sm‐hPAF recognizes both membrane cholesterol and huCD59 as receptors for triggering pore‐formation. Moreover, vaginolysin (VLY) of Gardnerella vaginalis showed similar characteristics to Sm‐hPAF regarding receptor recognition. On the basis of the results presented here, the mode of receptor recognition of CDCs can be categorized into the following three groups: (i) Group I, comprising typical CDCs with high affinity to cholesterol and no or very little affinity to huCD59; (ii) Group II, including atypical CDCs such as ILY, with no or very little affinity to cholesterol and high affinity to huCD59; and (iii) Group III, which contains atypical CDCs such as Sm‐hPAF and VLY with affinity to both cholesterol and huCD59.
Sustainably managing natural resources and the need for construction materials in Pacific island countries: The example of South Tarawa, Kiribati
Authors: Babinard Julie , Bennett Christopher R. , Hatziolos Marea E. , Faiz Asif , Somani Anil
Published: January 2014

The growing demand for construction materials in South Tarawa, a remote atoll in the South Pacific, provides an example of the environmental and social challenges associated with the use of non‐renewable resources in the context of small island countries threatened by coastal erosion and climate change. In many small Pacific island countries, the availability of construction materials is limited, with the majority mined from beaches and coastal reefs in an unsustainable manner. Growing demand for construction aggregates is resulting in more widespread sand mining by communities along vulnerable sections of exposed beach and reefs. This has serious consequences for coastal erosion and impacts on reef ecosystem processes, consequences that cannot be easily managed. Construction materials are also in high demand for infrastructure projects which are financed in part with support from international development agencies and donors. This paper reviews the various challenges and risks that aggregate mining poses to reefs, fish, and the coastal health of South Tarawa and argues that the long term consequences from ad hoc beach/reef mining over large areas are likely to be far greater than the impacts associated with environmentally sustainable, organized extraction. The paper concludes with policy recommendations that are also relevant for neighbouring island countries facing similar challenges.
Ultra‐deep Illumina sequencing accurately identifies MHC class IIb alleles and provides evidence for copy number variation in the guppy (Poecilia reticulata)
Authors: Lighten Jackie , van Oosterhout Cock , Paterson Ian G. , McMullan Mark , Bentzen Paul
Published: January 2014

We address the bioinformatic issue of accurately separating amplified genes of the major histocompatibility complex (MHC) from artefacts generated during high‐throughput sequencing workflows. We fit observed ultra‐deep sequencing depths (hundreds to thousands of sequences per amplicon) of allelic variants to expectations from genetic models of copy number variation (CNV). We provide a simple, accurate and repeatable method for genotyping multigene families, evaluating our method via analyses of 209 b of MHC class IIb exon 2 in guppies (Poecilia reticulata). Genotype repeatability for resequenced individuals (N = 49) was high (100%) within the same sequencing run. However, repeatability dropped to 83.7% between independent runs, either because of lower mean amplicon sequencing depth in the initial run or random PCR effects. This highlights the importance of fully independent replicates. Significant improvements in genotyping accuracy were made by greatly reducing type I genotyping error (i.e. accepting an artefact as a true allele), which may occur when using low‐depth allele validation thresholds used by previous methods. Only a small amount (4.9%) of type II error (i.e. rejecting a genuine allele as an artefact) was detected through fully independent sequencing runs. We observed 1–6 alleles per individual, and evidence of sharing of alleles across loci. Variation in the total number of MHC class II loci among individuals, both among and within populations was also observed, and some genotypes appeared to be partially hemizygous; total allelic dosage added up to an odd number of allelic copies. Collectively, observations provide evidence of MHC CNV and its complex basis in natural populations.
Fluvial archives as a framework for the Lower and Middle Palaeolithic: patterns of British artefact distribution and potential chronological implications
Authors: Bridgland David R. , White Mark J.
Published: January 2014

With the adoption of an ‘expanded chronology’ for the Middle Pleistocene, based on the greater number of warm and cold episodes evident in the marine oxygen isotope record from deep ocean cores, has come the recognition of a meaningful progression of artefact types, something that could not be achieved with reference to the previous ‘compressed chronology’. In Britain, at least, it has been established that Levallois knapping techniques appeared in MIS 9–8, that bout coupé handaxes are indicative of MIS 3 and, rather more tentatively, that assemblages with twisted ovate handaxes in significant numbers represent MIS 11 occupation. Added to these key markers, it is now possible to suggest that further tool types occur preferentially in deposits of particular age: assemblages with significant proportions of cleavers and ‘ficron’ handaxes appear to be correlated with deposits formed at around the time of the MIS 9 interglacial. This newly recognized patterning within the Lower and Middle Palaeolithic record differs markedly from the previous use, in the mid‐20th century, of archaeological typology as a means of dating Pleistocene sequences, which was based on a relative refinement of tool making that is now recognized to be unrelated to age. Indeed, the authors would wish to emphasize that, even with reference to the new scheme presented here, the archaeological record should only be seen as dating evidence ‘of last resort’.
Excess body mass is associated with T cell differentiation indicative of immune ageing in children
Authors: Spielmann G , Johnston C A , O'Connor D P , Foreyt J P , Simpson R J
Published: January 2014

Obesity has been associated with accelerated biological ageing and immunosenescence. As the prevalence of childhood obesity is increasing, we wanted to determine if associations between obesity and immunosenescence would manifest in children. We studied 123 Mexican American adolescents aged 10–14 (mean 12·3 ± 0·7) years, with body weights ranging from 30·1 to 115·2 kg (mean 52·5 ± 14·5 kg). Blood samples were obtained to determine proportions of naive, central memory (CM), effector memory (EM), senescent and early, intermediate and highly differentiated subsets of CD4+ and CD8+ T cells. Overweight and obese children had significantly lowered proportions of early CD8+ T cells (B = −11·55 and –5·51%, respectively) compared to healthy weight. Overweight children also had more EM (B = +7·53%), late (B = +8·90%) and senescent (B = +4·86%) CD8+ T cells than healthy weight children, while obese children had more intermediate CD8+ (B = +4·59%), EM CD8+ (B = +5·49%), late CD4+ (B = +2·01%) and senescent CD4+ (B = +0·98%) T cells compared to healthy weight children. These findings withstood adjustment for potentially confounding variables, including age, gender and latent cytomegalovirus and Epstein–Barr virus infections. We conclude that excess body mass, even in adolescence, may accelerate immunosenescence and predispose children to increased risks of incurring immune-related health problems in adulthood.
Microbial ‘old friends’, immunoregulation and socioeconomic status
Authors: Rook G A W , Raison C L , Lowry C A
Published: January 2014

The immune system evolved to require input from at least three sources that we collectively term the ‘old friends’: (i) the commensal microbiotas transmitted by mothers and other family members; (ii) organisms from the natural environment that modulate and diversify the commensal microbiotas; and (iii) the ‘old’ infections that could persist in small isolated hunter-gatherer groups as relatively harmless subclinical infections or carrier states. These categories of organism had to be tolerated and co-evolved roles in the development and regulation of the immune system. By contrast, the ‘crowd infections’ (such as childhood virus infections) evolved later, when urbanization led to large communities. They did not evolve immunoregulatory roles because they either killed the host or induced solid immunity, and could not persist in hunter-gatherer groups. Because the western lifestyle and medical practice deplete the ‘old’ infections (for example helminths), immunoregulatory disorders have increased, and the immune system has become more dependent upon microbiotas and the natural environment. However, urbanization maintains exposure to the crowd infections that lack immunoregulatory roles, while accelerating loss of exposure to the natural environment. This effect is most pronounced in individuals of low socioeconomic status (SES) who lack rural second homes and rural holidays. Interestingly, large epidemiological studies indicate that the health benefits of living close to green spaces are most pronounced for individuals of low SES. Here we discuss the immunoregulatory role of the natural environment, and how this may interact with, and modulate, the proinflammatory effects of psychosocial stressors in low SES individuals.
Examining the Structure of Opportunity and Social Mobility in India: Who Becomes an Engineer?
Authors: Krishna Anirudh
Published: January 2014

Rising inequality alongside rapid economic growth reinforces the need to examine patterns of social mobility in India. Are children from less well‐off sections also able to rise to higher‐paying positions, newly created by the growing economy, or are these positions mainly accessible to established elites? Powered in particular by the software industry, no sector has grown as fast as engineering in India. Examining the social origins of students at a range of engineering colleges, including higher‐ and lower‐ranked ones, provides a useful lens for understanding how the new opportunities have availed different social segments. These results provide some grounds for optimism: women, scheduled castes, and sons and daughters of agriculturists have improved upon historical trends. However, the rural–urban divide remains deep: the more rural one is, the lower are one's chances of getting into any engineering college. Multiple simultaneous handicaps — being poorandrural or scheduled casteandrural — reduce these chances to virtually zero. Improving education quality together with better information provision and more accessible career advice are critical for making opportunity more equitable.
ControlledEpstein–Barr virus reactivation after allogeneic transplantation is associated with improved survival
Authors: Auger Sophie , Orsini Mattea , Céballos Patrice , Fegueux Nathalie , Kanouni Tarik , Caumes Bastien , Klein Bernard , Villalba Martin , Rossi Jean‐François
Published: January 2014

Epstein–Barr virus reactivation (EBV‐R) frequently occurs in patients having allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the impact of controlledEBV‐Ron survival of 190 patients (114M/76F, median age: 51 yr, range 18–69), havingHSCTfor hematological malignancies (105 acute leukemias and myelodysplasias, 71 lymphoproliferative disorders, 14 others). Overall survival (OS) and progression‐free survival (PFS) were compared between patients with and withoutEBV‐R. Of 138, patients had reduced‐intensity conditioning regimen. Various stem cell sources (141PB, 33 umbilical cord blood and 16 bone marrow) were used. Patients withEBV‐Rhad longerPFSandOSthan those withoutEBV‐R:PFSat 2 yr 69% vs. 51% and at 5 yr 47% vs. 38% (P < 0.04);OSat 2 yr 76% vs. 64% and at 5 yr 63% vs. 47%) (P < 0.001). The use of rituximab had no impact onOSandPFS, but it reduced the intensity ofGVHD, despite the fact thatTRMwas not significantly different between the two groups of patients. So, rituximab may have an additional effect to other factors onPFSandOS. In multivariate analysis, antithymocyte globulin administration was not a significant factor forPFS(P = 0.68) and forOS(P = 0.81). CirculatingNKcells were significantly increased by 22% (P = 0.03) inEBV‐Rpatients with no differences for other parameters. ControlledEBV‐Rin the setting ofHSCTis associated with betterOSandPFS, with a significant increase in circulatingNKcells.
Effects of co‐creation claim on consumer brand perceptions and behavioural intentions
Authors: van Dijk Joyce , Antonides Gerrit , Schillewaert Niels
Published: January 2014

Increasingly often, companies ‘co‐create’ with consumers in open innovation practices to develop new products more effectively. Little is known about how co‐creation affects consumer brand perceptions in the mass market. We hypothesize that co‐creative brands – as opposed to non–co‐creative brands – are perceived as more authentic and sincere, and are associated with relatively positive behavioural intentions. A between‐subjects experiment was conducted to test these hypotheses in an online panel of consumers who did not take part in co‐creation. The experiment had a 3 (control vs. co‐creation vs. co‐creation supported with some visual proof) × 2 (well‐known existing brand vs. fictitious brand) design. Quantitative data analyses (n = 530) confirmed that for both brands, co‐creation affects brand personality perceptions directly and behavioural intentions indirectly. This study shows that co‐creating with consumers can be a strategic method to positively influence product perceptions and behavioural intentions.
A review of captive flamingo (Phoenicopteridae) welfare: a synthesis of current knowledge and future directions
Authors: Rose P. E. , Croft D. P. , Lee R.
Published: January 2014

Flamingos are ubiquitous captive species (potentially the world's most commonly kept zoo bird) that have long lifespans and unique breeding cycles. In‐depth research into the links between provision (enclosure, husbandry), behavioural performance (reflecting internal motivation) and perceived welfare state (from behavioural cues) can inform management for good welfare over the many decades of a bird's life, and benefit reproductive output. Here, the published literature on flamingo husbandry is reviewed, with reference to our current understanding of flamingo behaviour in the wild. Evaluation of whole‐flock time budgets and assessment of behavioural diversity can highlight any deviation from a norm. Several published works suggest ways of improving breeding success in captive flamingos by re‐evaluating husbandry routines as well as highlighting minimum numbers of birds per flock for ‘good welfare’. Research has shown that some aspects of zoo‐flamingo activity can match that of wild birds. Further examination of specific behaviour patterns, as well as the motivations for these, would allow for evidence‐based enclosure design and provision of species‐specific behavioural husbandry. Future research topics covering social support, foraging activity and developing a definition of ‘positive welfare activity’ would further enhance zoo management practices for these birds.
Morphological variation in vanishing Mexican desert fishes of the genus Characodon (Goodeidae)
Authors: Tobler M. , Bertrand N.
Published: January 2014

This study investigated a rapidly vanishing group of fishes in the genus Characodon (including Characodon lateralis and Characodon audax) from the upper Rio Mezquital drainage in Mexico. Using specimens from museum collections, morphological variation was assessed to quantify body shape differentiation among historic (i.e. extirpated and extant) collection sites. In both sexes, body shape (particularly head shape, the proportion of the caudal peduncle and the position and size of dorsal and anal fins) varied significantly among populations and species. Variation among collection sites could at least partially be attributed to geography, as the presence of distinct hydrographic units and a major waterfall coincided with major body shape differences. These results are discussed in the light of previously published molecular genetic analyses, as they have direct implications for taxonomic problems and the need for conservation measures for these endangered fishes.
Prevalence and potential determinants of musculoskeletal disease symptoms among care workers in long‐term care facilities in South Korea
Authors: Park Myung‐Sook , Yu Mi , Yu Su‐Jeong , Kang Kyung‐Ja , Seo Hyun‐Mi
Published: January 2014

Aim

The purpose of this study was to investigate the degree and influencing factors of musculoskeletal disease symptoms among care workers in long‐term care facilities in South Korea.

Methods

Participants in this cross‐sectional study were 265 care workers in 15 long‐term care facilities. Data were collected between 1 and 27 August 2011, using the Korea Occupational Safety and Health Agency (KOSHA) code H‐30–2003 and analyzed using logistic regression with SPSS ver. 18.0.

Results

Of the care workers, 88.7% had pain in at least one of the six body parts. The highest prevalence of musculoskeletal disease symptoms was in the lower back and legs. Among the organizational factors, there were significant differences in neck pain by work shift and patient grade. Neck pain was more severe in the 8 h shift group than 12–24 h shift group. Care workers caring for patients who were classified in the first patient grade of long‐term care insurance had 4.73 times more complaints of musculoskeletal symptoms in the neck, 9.54 times (95% confidence interval [CI] = 3.37–27.02) in the hand and wrist, 4.37 times (95% CI = 1.59–12.03) in the lower back, and 2.96 times (95% CI: 1.17–7.51) in the leg and foot.

Conclusion

To prevent and manage musculoskeletal disease symptoms, activities and the intensity of work should be arranged systematically and planned, and the improvement of organizational factors such as appropriate assignment by patients' severity is considered.
HpaP modulates type III effector secretion in Ralstonia solanacearum and harbours a substrate specificity switch domain essential for virulence
Authors: Lohou David , Turner Marie , Lonjon Fabien , Cazalé Anne‐Claire , Peeters Nemo , Genin Stéphane , Vailleau Fabienne
Published: January 2014

Many pathogenic bacteria have evolved a type III secretion system (T3SS) to successfully invade their host. This extracellular apparatus allows the translocation of proteins, called type III effectors (T3Es), directly into the host cells. T3Es are virulence factors that have been shown to interfere with the host's immunity or to provide nutrients from the host to the bacteria. The Gram‐negative bacterium Ralstonia solanacearum is a worldwide major crop pest whose virulence strongly relies on the T3SS. In R. solanacearum, transcriptional regulation has been extensively studied. However, very few data are available concerning the role played by type III‐associated regulators, such as type III chaperones and T3SS control proteins. Here, we characterized HpaP, a putative type III secretion substrate specificity switch (T3S4) protein of R. solanacearum which is not secreted by the bacterium or translocated in the plant cells. HpaP self‐interacts and interacts with the PopP1 T3E. HpaP modulates the secretion of early (HrpY pilin) and late (AvrA and PopP1 T3Es) type III substrates. HpaP is dispensable for the translocation of T3Es into the host cells. Finally, we identified two regions of five amino acids in the T3S4 domain that are essential for efficient PopP1 secretion and for HpaP's role in virulence on tomato and Arabidopsis thaliana, but not required for HpaP–HpaP and HpaP–PopP1 interactions. Taken together, our results indicate that HpaP is a putative R. solanacearum T3S4 protein important for full pathogenicity on several hosts, acting as a helper for PopP1 secretion, and repressing AvrA and HrpY secretion.
Clinicopathologic and electrocardiographic features of Akita dogs with high and low erythrocyte potassium phenotypes
Authors: Conrado Francisco O. , Oliveira Simone T. , Lacerda Luciana A. , Silva Mariana O. D. , Hlavac Nicole , González Félix H. D.
Published: January 2014

Background

CanineRBCs are expected to have high sodium and low potassium (LK) concentrations. However, some dogs have a low sodium and high potassium (HK) phenotype due to a Na‐K pump in the matureRBCmembrane. Awareness of this particularity avoids misinterpretation of hyperkalemia in affected dogs.

Objective

The purpose of this study was to compare theCBCs, serum biochemistry profiles, urinalysis data, and electrocardiography data inHKandLKAkita dogs.

Methods

In this study, the intra‐RBCpotassium (KRBC) was measured in 48 healthy adult Akita dogs. The HK group included dogs withKRBCconcentration at least 5‐fold that of plasma, while the LK dogs served as controls.

Results

TheHKphenotype was determined in 10 dogs (21%). With the exception of higher plasma potassium concentrations in theHKgroup compared withLKcontrols (6.6 mmol/L vs 4.4 mmol/L,P < .001), there were no other differences in serum biochemistry variables. In hematology, mean HGB concentration (13.5 vs 15.9,P < .001),PCV(42.9 vs 46.7,P = .009),RBC(6.1 vs 7.4,P < .001), andMCHC(31.3 vs 34.0,P < .001) were significantly lower in theHKgroup, whileMCV(70.0 vs 63.4,P < .001) was higher compared with theLKcontrols. There were no significant differences in urinalysis or electrocardiography data between groups.

Conclusions

HKAkita dogs showed significant differences in several hematologic variables, as well as higher plasma potassium concentration. Therefore, theHKphenotype should be considered in the interpretation of these variables in this breed.
The Association Between Changes in Speed Skating Technique and Changes in Skating Velocity
Authors: Noordhof Dionne A. , Foster Carl , Hoozemans Marco J.M. , de Koning Jos J.
Published: January 2014

A meaningful association between changes (Δ) in push-off angle or effectiveness (e) and changes in skating velocity (v) has been found during 5000-m races, although no significant association was found between changes in knee (θ0) and trunk angle (θ1) and Δv. It might be that speed skating event, sex, and performance level influence these associations.

Purpose:

To study the effect of skating event, sex, and performance level on the association between Δe and Δv and between Δθ0 and Δθ1 and Δv.

Methods:

Video recordings were made from frontal (e) and sagittal views (θ0 and θ1) during 1500- and 5000-m men’s and women’s World Cup races. Radio-frequency identification tags provided data of v.

Results:

Skating event influenced the association between Δe and Δv, which resulted in a significant association between Δe and Δv for the 5000-m (β = –0.069, 95% confidence interval [–0.11, –0.030]) but not for the 1500-m (β = –0.011 [–0.032, 0.010]). The association between Δθ0 and Δθ1 and Δv was not significantly influenced by skating event. Sex and performance level did not substantially affect the association between Δe and Δv and between Δθ0 and Δθ1 and Δv.

Conclusions:

Skating event significantly influenced the association between Δe and Δv; a 1° change in e results in a 0.011-m/s decrease in v during the 1500-m and a 0.069-m/s decrease in v during the 5000-m. Thus, it seems especially important to maintain a small e during the 5000-m.
A Common Polymorphism of the MCT1 Gene and Athletic Performance
Authors: Fedotovskaya Olga N. , Mustafina Leysan J. , Popov Daniil V. , Vinogradova Olga L. , Ahmetov Ildus I.
Published: January 2014

Purpose:

In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79).

Methods:

Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer.

Results:

Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005).

Conclusions:

MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.
Aerobic and Anaerobic Contributions to Energy Production Among Junior Male and Female Cross-Country Skiers During Diagonal Skiing
Authors: McGawley Kerry , Holmberg Hans-Christer
Published: January 2014

Purpose:

Cross-country-ski races place complex demands on athletes, with events lasting between approximately 3 min and 2 h. The aim of the current study was to compare the aerobic and anaerobic measures derived from a short time trial (TT) between male and female skiers using diagonal cross-country skiing.

Methods:

Twenty-four highly trained cross-country skiers (12 male and 12 female, age 17.4 ± 1.4 y, body mass 68.2 ± 8.9 kg, height 174 ± 8 cm) participated. The submaximal VO2–speed relationship and VO2max were derived from an incremental ramp test to exhaustion (RAMP), while the accumulated oxygen deficit (AOD), peak VO2, and performance time were measured during a 600-m TT.

Results:

The female skiers took longer to complete the TT than the males (209 ± 9 s vs 166 ± 7 s, P < .001) and exhibited a lower relative anaerobic contribution (20% ± 4% vs 24% ± 3%, P = .015) and a higher fractional utilization of VO2max (84% ± 4% vs 79% ± 5%, P = .007) than males. Although there was no significant difference in AOD between the sexes (40.9 ± 9.5 and 47.3 ± 7.4 mL/kg for females and males, respectively; P = .079), the mean difference ± 90% confidence intervals of 6.4 ± 6.0 mL/kg reflected a likely practical difference (ES = 0.72). The peak VO2 during the TT was significantly higher than VO2max during the RAMP for all participants combined (62.3 ± 6.8 vs 60.5 ± 7.2 mL · kg−1 · min−1, P = .011), and the mean difference ± 90% confidence intervals of 1.8 ± 1.1 mL · kg−1 · min−1 reflected a possible practical difference (ES = 0.25).

Conclusions:

These results show that performance and physiological responses to a self-paced TT lasting approximately 3 min differ between sexes. In addition, a TT may provide a valid measure of VO2max.
Changes in Technique and Efficiency After High-Intensity Exercise in Cross-Country Skiers
Authors: Grasaas Christina Åsan , Ettema Gertjan , Hegge Ann Magdalen , Skovereng Knut , Sandbakk Øyvind
Published: January 2014

This study investigated changes in technique and efficiency after high-intensity exercise to exhaustion in elite cross-country skiers. Twelve elite male skiers completed 4 min submaximal exercise before and after a high-intensity incremental test to exhaustion with the G3 skating technique on a 5% inclined roller-ski treadmill. Kinematics and kinetics were monitored by instrumented roller skis, work rate was calculated as power against roller friction and gravity, aerobic metabolic cost was determined from gas exchange, and blood lactate values indicated the anaerobic contribution. Gross efficiency was the work rate divided by aerobic metabolic rate. A recovery period of 10 min between the incremental test and the posttest was included to allow the metabolic values to return to baseline. Changes in neuromuscular fatigue in upper and lower limbs before and after the incremental test were indicated by peak power in concentric bench press and squat-jump height. From pretest to posttest, cycle length decreased and cycle rate increased by approximately 5% (P < 0.001), whereas the amount of ski forces did not change significantly. Oxygen uptake increased by 4%, and gross efficiency decreased from 15.5% ± 0.7% to 15.2% ± 0.5% from pretest to posttest (both P < .02). Correspondingly, blood lactate concentration increased from 2.4 ± 1.0 to 6.2 ± 2.5 mmol/L (P < .001). Bench-press and squat-jump performance remained unaltered. Elite cross-country skiers demonstrated a less efficient technique and shorter cycle length during submaximal roller-ski skating after high-intensity exercise. However, there were no changes in ski forces or peak power in the upper and lower limbs that could explain these differences.
Can Cancer Trigger Autoimmunity?
Authors: Teng Michele W. L. , Smyth Mark J.
Published: January 2014

A chronic autoimmune disease sometimes appears coincidently in patients with cancer.

[Also see Research Article by

Joseph
et al.

]
A Pancreas in a Box
Authors: Clery Daniel
Published: January 2014

Sophisticated sensors, insulin pumps, and algorithms may help give type 1 diabetics a more normal life while researchers work on a cure.
B-Cell-Specific Peptides of Leptospira interrogans LigA for Diagnosis of Patients with Acute Leptospirosis
Authors: Kanagavel Murugesan , Shanmughapriya Santhanam , Anbarasu Kumarasamy , Natarajaseenivasan Kalimuthusamy
Published: January 2014

Leptospirosis is a reemerging infectious disease that is underdiagnosed and under-recognized due to low-sensitivity and cumbersome serological tests. Rapid reliable alternative tests are needed for early diagnosis of the disease. Considering the importance of the pathogenesis-associated leptospiral LigA protein expressedin vivo, we have evaluated its application in the diagnosis of the acute form of leptospirosis. The C-terminal coding sequence ofligA(ligA-C) was cloned into pET15b and expressed inEscherichia coli. Furthermore, the B-cell-specific epitopes were predicted and were synthesized as peptides for evaluation along with recombinant LigA-C. Epitope 1 (VVIENTPGK), with a VaxiJen score of 1.3782, and epitope 2 (TALSVGSSK), with a score of 1.2767, were utilized. A total of 140 serum samples collected from leptospirosis cases during the acute stage of the disease and 138 serum samples collected from normal healthy controls were utilized for evaluation. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the recombinant LigA-C-specific IgM enzyme-linked immunosorbent assay (ELISA) and were found to be 92.1%, 97.7%, 92.8%, and 97.5%, respectively. Epitopes 1 and 2 used in the study showed 5.1 to 5.8% increased sensitivity over recombinant LigA-C in single and combination assays for IgM antibody detection. These findings suggest that these peptides may be potential candidates for the early diagnosis of leptospirosis.
Impact of New Antifungal Breakpoints on Antifungal Resistance in Candida Species
Authors: Fothergill Annette W. , Sutton Deanna A. , McCarthy Dora I. , Wiederhold Nathan P.
Published: January 2014

We reviewed our antifungal susceptibility data for micafungin, anidulafungin, fluconazole, and voriconazole against
Candida
species and compared resistance rates determined by the previous and recently revised CLSI antifungal breakpoints. With the new breakpoints, resistance was significantly increased for micafungin (from 0.8% to 7.6%), anidulafungin (from 0.9% to 7.3%), and voriconazole (from 6.1% to 18.4%) against
Candida glabrata
. Resistance was also increased for fluconazole against
Candida albicans
(from 2.1% to 5.7%).
The Nef-Like Effect of Murine Leukemia Virus Glycosylated Gag on HIV-1 Infectivity Is Mediated by Its Cytoplasmic Domain and Depends on the AP-2 Adaptor Complex
Authors: Usami Yoshiko , Popov Sergei , Göttlinger Heinrich G.
Published: January 2014

Human immunodeficiency virus type 1 (HIV-1) Nef enhances the infectivity of progeny virions. However, Nef is dispensable for the production of HIV-1 virions of optimal infectivity if the producer cells are superinfected with certain gammaretroviruses. In the case of the ecotropic Moloney murine leukemia virus (M-MLV), the Nef-like effect is mediated by the glycosylated Gag (glycoGag) protein. We now show that the N-terminal intracellular domain of the type II transmembrane protein glycoGag is responsible for its effect on HIV-1 infectivity. In the context of a fully active minimal M-MLV glycoGag construct, truncations of the cytoplasmic domain led to a near total loss of activity. Furthermore, the cytoplasmic domain of M-MLV glycoGag was fully sufficient to transfer the activity to an unrelated type II transmembrane protein. Although the intracellular region of glycoGag is relatively poorly conserved even among ecotropic and xenotropic MLVs, it was also fully sufficient for the rescue of
nef
-deficient HIV-1 when derived from a xenotropic virus. A mutagenic analysis showed that only a core region of the intracellular domain that exhibits at least some conservation between murine and feline leukemia viruses is crucial for activity. In particular, a conserved YXXL motif in the center of this core region was critical. In addition, expression of the μ2 subunit of the AP-2 adaptor complex in virus producer cells was essential for activity. We conclude that the ability to enhance HIV-1 infectivity is a conserved property of the MLV glycoGag cytoplasmic domain and involves AP-2-mediated endocytosis.

IMPORTANCE
The Nef protein of HIV-1 and the entirely unrelated glycosylated Gag (glycoGag) protein of a murine leukemia virus (MLV) similarly enhance the infectiousness of HIV-1 particles by an unknown mechanism. MLV glycoGag is an alternative version of the structural viral Gag protein with an extra upstream region that provides a cytosolic domain and a plasma membrane anchor. We now show for the first time that the cytosolic domain of MLV glycoGag contains all the information needed to enhance HIV-1 infectivity and that this function of the cytosolic domain is conserved despite limited sequence conservation. Within the cytosolic domain, a motif that resembles a cellular sorting signal is critical for activity. Furthermore, the enhancement of HIV-1 infectivity depends on an endocytic cellular protein that is known to interact with such sorting signals. Together, our findings implicate the endocytic machinery in the enhancement of HIV-1 infectivity by MLV glycoGag.
Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients
Authors: Nogueira Raul G , Gupta Rishi , Jovin Tudor G , Levy Elad I , Liebeskind David S , Zaidat Osama O , Rai Ansaar , Hirsch Joshua A , Hsu Daniel P , Rymer Marilyn M , Tayal Ashis H , Lin Ridwan , Natarajan Sabareesh K , Nanda Ashish , Tian Melissa , Hao Qing , Kalia Junaid S , Chen Michael , Abou-Chebl Alex , Nguyen Thanh N , Yoo Albert J
Published: January 2014

Background and purpose

Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy.

Methods

Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality.

Results

There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13–20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001).

Conclusions

Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the ‘benign’ nature of HI suggested by earlier studies.
Endovascular repair of direct carotid–cavernous fistula in Ehlers–Danlos type IV
Authors: Linfante Italo , Lin Eugene , Knott Eric , Katzen Barry , Dabus Guilherme
Published: January 2014

Ehlers–Danlos syndrome (EDS) type IV is a collagen vascular disease with an autosomal dominant inheritance caused by COL3A1 mutation. Patients with EDS type IV can present with organ rupture, spontaneous arterial dissections and ruptured aneurysms. Because of their propensity to form arterial dissections, aneurysms and rupture, they can develop carotid–cavernous fistula (CCF) after minor trauma or spontaneously. In EDS, it has been reported that even conventional catheter diagnostic angiography may result in large artery dissections and vessel rupture. In addition, the treatment of CCF in EDS type IV can result in up to 59% mortality after initial treatment, of which 23% is attributed to direct complications of treatment. We present the case of a patient with EDS type IV who previously had spontaneous dissection and multiple pseudoaneurysms of both the iliac and femoral arteries and the distal abdominal aorta. Several years later the patient developed a direct type A CCF which was successfully treated with endovascular embolization using a transvenous approach with detachable coils. The literature pertaining to CCF in EDS type IV and its treatment is reviewed.
3-(2-Bromovinyl)chlorins: a new approach towards chlorophyll a modification
Authors: Lonin Ivan S. , Kuzovlev Andrey S. , Belyaev Evgeny S. , Ponomarev Gelii V. , Koifman Oskar I. , Tsivadze Aslan Yu.
Published: January 2014

Regioselective bromination of methyl pyropheophorbide a at the C32-position of the terminal double bond has been carried out as a one-pot two-step addition/elimination process. The elimination occurs with 100% stereoselectivity and bromovinyl 4 has E-configuration of the C3-double bond. The reactivity of unsaturated bromide 4 has been evaluated in the series of the Pd -catalyzed coupling reactions.
Na+/H+and Na+/NH4+exchange activities of zebrafish NHE3b expressed inXenopusoocytes
Authors: Ito Yusuke , Kato Akira , Hirata Taku , Hirose Shigehisa , Romero Michael F.
Published: January 2014

Zebrafish Na+/H+exchanger 3b (zNHE3b) is highly expressed in the apical membrane of ionocytes where Na+is absorbed from ion-poor fresh water against a concentration gradient. Much in vivo data indicated that zNHE3b is involved in Na+absorption but not leakage. However, zNHE3b-mediated Na+absorption has not been thermodynamically explained, and zNHE3b activity has not been measured. To address this issue, we overexpressed zNHE3b in Xenopus oocytes and characterized its activity by electrophysiology. Exposure of zNHE3b oocytes to Na+-free media resulted in significant decrease in intracellular pH (pHi) and intracellular Na+activity ( aNai). aNaiincreased significantly when the cytoplasm was acidified by media containing CO2-HCO3−or butyrate. Activity of zNHE3b was inhibited by amiloride or 5-ethylisopropyl amiloride (EIPA). Although the activity was accompanied by a large hyperpolarization of ∼50 mV, voltage-clamp experiments showed that Na+/H+exchange activity of zNHE3b is electroneutral. Exposure of zNHE3b oocytes to medium containing NH3/NH4+resulted in significant decreases in pHiand aNaiand significant increase in intracellular NH4+activity, indicating that zNHE3b mediates the Na+/NH4+exchange. In low-Na+(0.5 mM) media, zNHE3b oocytes maintained aNaiof 1.3 mM, and Na+-influx was observed when pHiwas decreased by media containing CO2-HCO3−or butyrate. These results provide thermodynamic evidence that zNHE3b mediates Na+absorption from ion-poor fresh water by its Na+/H+and Na+/NH4+exchange activities.
Acute inhibition of NCC does not activate distal electrogenic Na+reabsorption or kaliuresis
Authors: Hunter Robert W. , Craigie Eilidh , Homer Natalie Z. M. , Mullins John J. , Bailey Matthew A.
Published: January 2014

Na+reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na+channel (ENaC) downstream. This effect might be mediated by changes in distal Na+delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na+flux through ENaC, with a concomitant increase in renal K+excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K+excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na+reabsorption was not normally limited by Na+delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na+restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na+reabsorption through ENaC solely by increasing distal Na+delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.