bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific Arabidopsis thaliana malic enzyme isoforms can provide anaplerotic pyruvate carboxylation function in Saccharomyces cerevisiae
Authors: Badia Mariana Beatriz , Mans Robert , Lis Alicia V. , Tronconi Marcos Ariel , Arias Cintia Lucía , Maurino Verónica Graciela , Andreo Carlos Santiago , Drincovich María Fabiana , van Maris Antonius J. A. , Gerrard Wheeler Mariel Claudia
Published: January 2017

NAD(P)‐malic enzyme (NAD(P)‐ME) catalyzes the reversible oxidative decarboxylation of malate to pyruvate, CO2, and NAD(P)H and is present as a multigene family in Arabidopsis thaliana. The carboxylation reaction catalyzed by purified recombinant Arabidopsis NADP‐ME proteins is faster than those reported for other animal or plant isoforms. In contrast, no carboxylation activity could be detected in vitro for the NAD‐dependent counterparts. In order to further investigate their putative carboxylating role in vivo, Arabidopsis NAD(P)‐ME isoforms, as well as the NADP‐ME2del2 (with a decreased ability to carboxylate pyruvate) and NADP‐ME2R115A (lacking fumarate activation) versions, were functionally expressed in the cytosol of pyruvate carboxylase‐negative (Pyc−) Saccharomyces cerevisiae strains. The heterologous expression of NADP‐ME1, NADP‐ME2 (and its mutant proteins), and NADP‐ME3 restored the growth of Pyc− S. cerevisiae on glucose, and this capacity was dependent on the availability of CO2. On the other hand, NADP‐ME4, NAD‐ME1, and NAD‐ME2 could not rescue the Pyc− strains from C4 auxotrophy. NADP‐ME carboxylation activity could be measured in leaf crude extracts of knockout and overexpressing Arabidopsis lines with modified levels of NADP‐ME, where this activity was correlated with the amount of NADP‐ME2 transcript. These results indicate that specific A. thaliana NADP‐ME isoforms are able to play an anaplerotic role in vivo and provide a basis for the study on the carboxylating activity of NADP‐ME, which may contribute to the synthesis of C4 compounds and redox shuttling in plant cells.
Extreme rainfall and snowfall alter responses of soil respiration to nitrogen fertilization: a 3‐year field experiment
Authors: Chen Zengming , Xu Yehong , Zhou Xuhui , Tang Jianwu , Kuzyakov Yakov , Yu Hongyan , Fan Jianling , Ding Weixin
Published: January 2017

Extreme precipitation is predicted to be more frequent and intense accompanying global warming and may have profound impacts on soil respiration (Rs) and its components, that is, autotrophic (Ra) and heterotrophic (Rh) respiration. However, how natural extreme rainfall or snowfall events affect these fluxes are still lacking, especially under nitrogen (N) fertilization. In this study, extreme rainfall and snowfall events occurred during a 3‐year field experiment, allowing us to examine their effects on the response of Rs, Rh, and Ra to N supply. In normal rainfall years of 2011/2012 and 2012/2013, N fertilization significantly stimulated Rs by 23.9% and 10.9%, respectively. This stimulation was mainly due to the increase of Ra because of N‐induced increase in plant biomass. In the record wet year of 2013/2014, however, Rs was independent on N supply because of the inhibition effect of the extreme rainfall event. Compared with those in other years, Rh and Ra were reduced by 36.8% and 59.1%, respectively, which were likely related to the anoxic stress on soil microbes and decreased photosynthates supply. Although N supply did not affect annual Rh, the response ratio (RR) of Rh flux to N fertilization decreased firstly during growing season, increased in nongrowing season and peaked during spring thaw in each year. Nongrowing season Rs and Rh contributed 5.5–16.4% to their annual fluxes and were higher in 2012/2013 than other years due to the extreme snowfall inducing higher soil moisture during spring thaw. The RR of nongrowing season Rs and Rh decreased in years with extreme snowfall or rainfall compared to those in normal years. Overall, our results highlight the significant effects of extreme precipitation on responses of Rs and its components to N fertilization, which should be incorporated into models to improve the prediction of carbon‐climate feedbacks.
Long‐term enhanced winter soil frost alters growing season CO2 fluxes through its impact on vegetation development in a boreal peatland
Authors: Zhao Junbin , Peichl Matthias , Nilsson Mats B.
Published: January 2017

At high latitudes, winter climate change alters snow cover and, consequently, may cause a sustained change in soil frost dynamics. Altered winter soil conditions could influence the ecosystem exchange of carbon dioxide (CO2) and, in turn, provide feedbacks to ongoing climate change. To investigate the mechanisms that modify the peatland CO2 exchange in response to altered winter soil frost, we conducted a snow exclusion experiment to enhance winter soil frost and to evaluate its short‐term (1–3 years) and long‐term (11 years) effects on CO2 fluxes during subsequent growing seasons in a boreal peatland. In the first 3 years after initiating the treatment, no significant effects were observed on either gross primary production (GPP) or ecosystem respiration (ER). However, after 11 years, the temperature sensitivity of ER was reduced in the treatment plots relative to the control, resulting in an overall lower ER in the former. Furthermore, early growing season GPP was also lower in the treatment plots than in the controls during periods with photosynthetic photon flux density (PPFD) ≥800 μmol m−2 s−1, corresponding to lower sedge leaf biomass in the treatment plots during the same period. During the peak growing season, a higher GPP was observed in the treatment plots under the low light condition (i.e. PPFD 400 μmol m−2 s−1) compared to the control. As Sphagnum moss maximizes photosynthesis at low light levels, this GPP difference between the plots may have been due to greater moss photosynthesis, as indicated by greater moss biomass production, in the treatment plots relative to the controls. Our study highlights the different responses to enhanced winter soil frost among plant functional types which regulate CO2 fluxes, suggesting that winter climate change could considerably alter the growing season CO2 exchange in boreal peatlands through its effect on vegetation development.
Clonal reticulohistiocytosis of the skin and bone marrow associated with systemic mastocytosis and acute myeloid leukaemia
Authors: Fusco Nicola , Bonometti Arturo , Augello Claudia , Fabris Sonia , Boiocchi Leonardo , Fiori Stefano , Morotti Denise , Fracchiolla Nicola , Berti Emilio , Gianelli Umberto
Published: January 2017

Aims

The aims of this study were to define whether diffuse cutaneous reticulohistiocytosis could be underpinned by somatic genetic alterations and represent a precursor of more aggressive forms of disease.

Methods and results

A 59‐year‐old man with diffuse cutaneous reticulohistiocytosis experienced bone marrow localization of the disease, with associated systemic mastocytosis and acute myeloid leukaemia. Cytogenetic analyses of the bone marrow aspirate revealed the presence of a derivative chromosome giving rise to a partial trisomy of chromosome 1q and a partial monosomy of chromosome 9q. Therefore, we characterized the cutaneous lesions before and after chemotherapy by using an integrative approach combining histopathology, electron microscopy, and fluorescence in‐situ hybridization. Histologically, the skin lesions belonged to the spectrum of diffuse cutaneous reticulohistiocytoses, as confirmed by immunohistochemistry and ultrastructural analyses. Fluorescence in‐situ hybridization in the skin nodules confirmed the presence of the genetic alterations previously detected in the bone marrow.

Conclusions

Here, we provide circumstantial evidence to suggest that at least a subset of cutaneous reticulohistiocytoses harbour clonal molecular alterations. Furthermore, we confirm that these lesions have the potential to arise in the setting of concurrent haematological disorders. In this hypothesis‐generating study, two possible tumorigenesis models are proposed.
Fighting Corruption by Means of Effective Internal Audit Function: Evidence from the Ghanaian Public Sector
Authors: Asiedu Kofi Fred , Deffor Eric Worlanyo
Published: January 2017

Using structural equation modelling (SEM) we analysed the link between corruption and effective internal audit function (EIAF) in Ghana through a survey of directors and managers of selected public sector organizations. A decade after the promulgation of the Internal Audit Agency Act (IAAA), 2003 (Act 658) as an instrument to fight administrative corruption in Ghana, there is little empirical evidence to show its impact on corruption, though anecdotal evidence suggests it has played a critical role in maintaining financial discipline and public sector accountability and transparency. We established that full implementation of Act 658, size of the internal audit department and independence of the audit department significantly affect the effectiveness of the internal audit function which negatively impact on corruption. We conclude that strict adherence to and the implementation of regulations and laws as well as independence of the internal audit function will help fight administrative corruption in Ghana.
Providing opportunistic immunisations for at‐risk inpatients in a tertiary paediatric hospital
Authors: Elia Sonja , Perrett Kirsten , Newall Fiona
Published: January 2017

Attaining high immunisation coverage rates for children with medical conditions is vital. The Royal Children's Hospital (RCH) Immunisation Service has the opportunity to check each inpatient's immunisation status and provide opportunistic vaccines and/or bring the Australian Childhood Immunisation Register (ACIR) up‐to‐date. This paper highlights that during admission, one quarter of children were not up‐to‐date with routine scheduled immunisations and 42% of those inpatients due or overdue for immunisation were vaccinated. The model of establishing routine checking of immunisation records and reminding hospital staff about immunisation can result in improvements in vaccination coverage. Healthcare providers have a responsibility to check immunisation status and offer vaccines when necessary; however, often there are missed opportunities to immunise. This paper demonstrates that having a dedicated Immunisation Service, a partnership with a relevant government agency, and effective collaboration with inpatient clinical teams, opportunistic immunisation can be achieved for inpatients.
Analogy in Thomas Aquinas and Ludwig Wittgenstein. A comparison
Authors: Drescher Frank
Published: January 2017

The purpose of this essay is to illustrate the concept of analogy in the late works of St. Thomas Aquinas, i.e., in his two Summas, and to go on to compare this with Ludwig Wittgenstein's concept of “family resemblance” (“Familienähnlichkeit”), in order to reveal some interesting similarities between the named linguistic‐philosophical concepts of these two very different thinkers.
Double immunostaining for maspin and p53 on cell blocks increases the diagnostic value of biliary brushing cytology
Authors: Kanzawa Maki , Sanuki Tsuyoshi , Onodera Manabu , Fujikura Kohei , Itoh Tomoo , Zen Yoh
Published: January 2017

Our objective is to elucidate the usefulness of maspin/p53 double immunostaining on biliary brushing cytology specimens. We first examined the expression of maspin in the biliary epithelium with variable degrees of dysplasia using surgically resected specimens (n = 56). Maspin appeared to be overexpressed in a stepwise manner from benign to malignant cholangiocytes: the reactive epithelium (20%), biliary intraepithelial neoplasia (~50%), and invasive cholangiocarcinomas (>90%). Next, an automated sequential double immunostaining protocol for maspin and p53 was applied to paraffin‐embedded cell blocks of the biliary brushing cytology specimens obtained from 58 consecutive patients. Cell block preparation was successful in 44 cases (76%), which were morphologically diagnosed as adenocarcinoma (n = 16), atypical cells not diagnostic for malignancy (n = 10), and benign (n  = 18). Double positive cells were observed in 14/16 (88%) morphologically malignant, 6/10 (60%) borderline, and 0/18 benign cases. All 20 positive cases were proven to have pancreatobiliary malignancies by subsequent imaging or pathological analyses. A similar staining protocol for S100P and p53 was also applied to the same cohort; however, the positive frequency was slightly lower than those of maspin and p53 (36% vs. 45%). In conclusion, Maspin/p53 double immunostaining on cell blocks contributes to the detection of malignant cells in biliary brushing cytology specimens.
Classifying Gestational Weight Gain Trajectories Using theSITARGrowth Model
Authors: Riddell Corinne A , Platt Robert W. , Bodnar Lisa M. , Hutcheon Jennifer A.
Published: January 2017

Background

Gestational weight gain is often characterized by the total amount of weight gained during pregnancy, however, the pattern of gain may be an important determinant of health outcomes. TheSITAR(Super Imposition by Translation And Rotation) model has been used to describe childhood growth trajectories and has appeal because of the biological interpretability of its parameters. The objective of this study was to determine the feasibility of applying this model to gestational weight gain trajectories.

Methods

The study cohort included 3470 normal‐weight, overweight, and obese women delivering at Magee‐Womens Hospital in Pittsburgh, Pennsylvania, 1998 to 2010. We applied theSITARmodel, a non‐linear mixed effects model, to serial prenatal weight gain measurements in each pre‐pregnancy body mass index (BMI) category. We fit models of varying complexity, and chose the best‐fitting model to describe the pattern of weight gain (by its absolute amount, timing, and acceleration) for eachBMIgroup.

Results

The most complexSITARmodels failed to converge, but reduced models could successfully be fit by specifying fewer random effects and simplifying the modelling of gestational age. Best‐fitting models for eachBMIgroup explained between 95% and 97% of the variation in weight gain trajectories. Peak rates of weight gain were reached between the 20th and 22nd weeks, and were higher for normal and overweight women (0.59 kg/week and 0.57 kg/week, respectively) than obese women (0.46 kg/week).

Conclusions

Following some modifications, theSITARmodel can be used to characterize pregnancy weight gain patterns.
Light, temperature and tocopherol status influence foliar vascular anatomy and leaf function in Arabidopsis thaliana
Authors: Stewart Jared J. , Polutchko Stephanie K. , Adams William W. , Cohu Christopher M. , Wenzl Coleman A. , Demmig‐Adams Barbara
Published: January 2017

This study addressed whether the winter annual Arabidopsis thaliana can adjust foliar phloem and xylem anatomy both differentially and in parallel. In plants acclimated to hot vs cool temperature, foliar minor vein xylem‐to‐phloem ratio was greater, whereas xylem and phloem responded concomitantly to growth light intensity. Across all growth conditions, xylem anatomy correlated with transpiration rate, while phloem anatomy correlated with photosynthetic capacity for two plant lines (wild‐type Col‐0 and tocopherol‐deficient vte1 mutant) irrespective of tocopherol status. A high foliar vein density (VD) was associated with greater numbers and cross‐sectional areas of both xylem and phloem cells per vein as well as higher rates of both photosynthesis and transpiration under high vs low light intensities. Under hot vs cool temperature, high foliar VD was associated with a higher xylem‐to‐phloem ratio and greater relative rates of transpiration to photosynthesis. Tocopherol status affected development of foliar vasculature as dependent on growth environment. The most notable impact of tocopherol deficiency was seen under hot growth temperature, where the vte1 mutant exhibited greater numbers of tracheary elements (TEs) per vein, a greater ratio of TEs to sieve elements, with smaller individual sizes of TEs, and resulting similar total areas of TEs per vein and transpiration rates compared with Col‐0 wild‐type. These findings illustrate the plasticity of foliar vascular anatomy acclimation to growth environment resulting from independent adjustments of the vasculature's components.
Evolution of UhpC‐type hexose‐phosphate transporters in dinoflagellates
Authors: Hirakawa Yoshihisa , Nakayama Takuro , Keilert Nadine , Ishida Ken‐ichiro
Published: January 2017

Primary plastids of the group Archaeplastida are descendants of a single cyanobacterial endosymbiont, while many other algal groups have obtained complex plastids, the so‐called secondary plastids, via several parallel endosymbiotic uptakes of primary plastid‐bearing algae. Integration of the endosymbiont into its host during primary and secondary endosymbiosis necessitated the establishment of transport mechanisms for metabolites, inorganic ions, and proteins across plastid envelope membranes. As a potential protein for exporting photosynthates out of primary plastids, homologs of bacterial UhpC‐type hexose‐phosphate transporters were found in algal members of the Archaeplastida. It has been proposed that plastidic UhpC‐type transporters have been acquired in the common ancestor of Archaeplastida by the lateral gene transfer from a bacterial lineage closely related to Chlamydiae. However, it remains unknown whether secondary plastid‐bearing organisms possess UhpC‐type transporters. In the present study, we investigated homologous genes of UhpC in diverse algae using available genome and transcriptome data. Our homology survey and phylogenetic analyses revealed that only dinoflagellates possess UhpC‐type transporters derived from an archaeplastidal lineage, whereas many other secondary plastid‐bearing organisms lack them. It is possible that UhpC‐type transporters are not essential in many secondary plastids because of the existence of other families of sugar phosphate transporters.
Self‐Determination and Sovereignty over Natural Resources
Authors: Angeli Oliviero
Published: January 2017

This article makes the normative case for a differentiated approach to the sovereignty of states over natural resources. In the first half of the article, drawing on the example of the Yasuní‐ITT‐Initiative, I will argue that countries commit a moral wrong when they exploit natural resources for their own benefit (and to the detriment of the climate), but that they have the moral right to do so given the current structure of the international system. In the second half of the article, I address the question of whether states' rights over natural resources can be justified. Central to my argument will be the distinction between “control rights” and “income rights.” Only control rights, I will argue, can be justified as inherently tied to collective self‐determination.
The rise of the Brazilian Network for Ecological Restoration (REBRE): what Brazilian restorationists have learned from networking
Authors: Isernhagen Ingo , Moraes Luiz Fernando Duarte , Engel Vera Lex
Published: January 2017

As ecological restoration is gaining importance worldwide, researchers, practitioners, and interested people are beginning to self‐organize, in order to exchange knowledge and experiences in this growing area. Latin America has recently shown some examples, and the Brazilian Network for Ecological Restoration (REBRE) is one of them. Working on a nonhierarchical basis, its members, some of whom are important actors in the proposing and implementing of public policies, are able to freely express their doubts and share experiences, thereby contributing to legislative improvements, developing relevant restoration initiatives, and adopting novel approaches and paradigms. Through its three main communication platforms (website, Google Groups, and Facebook), REBRE has reached more than 2,300 members, and although a more equitable distribution through Brazilian regions should still be reached, it is gradually becoming stronger and more representative. In this scenario, REBRE will act with its branch organization, SOBRE (Brazilian Society for Ecological Restoration), to host the next Society for Ecological Restoration Conference, to be held in Brazil, in 2017, exchanging relevant experiences and welcoming restorationists from all over the world.
Full‐length sequence of 2 HLA‐B alleles, B*52:01:01:01 and B*52:01:02:01, identified by cloning and sequencing
Authors: Li Z. , Zou H.‐Y.
Published: January 2017

Full‐length sequence of
HLA‐B*52:01:01:01 and B*52:01:02:01, identified by cloning and sequencing in Chinese donors.
Use of an intravenous sclerosing foam (3% sodium tetradecyl sulfate) for treatment of orbital varix in a dog
Authors: Saunders Rebecca S. , Scansen Brian A. , Jung Stephen S. , Khabiri Hooman , Wilkie David A.
Published: January 2017

A 6‐month‐old intact male Standard Dachshund was referred for evaluation of a soft tissue swelling above the right eye. Examination of the right eye revealed mild lateral deviation of the globe, normal vision, and a dorsonasal soft tissue swelling. Examination of the posterior segment was normal. Dual‐phase computed tomography angiography was consistent with an orbital varix of the angularis oculi and right dorsal external ophthalmic veins with no evidence of arterial involvement. Treatment involved fluoroscopically guided coil embolization of the venous outflow with nine platinum microcoils, followed by sclerotherapy of the varix using 1.5 mL of 3% sodium tetradecyl sulfate foam. Moderate‐to‐marked swelling was noted at the treatment site in the weeks following therapy, which gradually resolved. At final reexamination 3 months post‐therapy, complete sclerosis and resolution of the orbital varix were documented. To the authors’ knowledge, this is the first reported case involving the use of a sclerotic agent for successful treatment of a venous malformation in a dog.
Effect of dorsal laminectomy and dorsal annulectomy with partial lumbosacral discectomy on the volume of the lateral intervertebral neuroforamina in dogs when the lumbosacral junction is extended
Authors: Worth Andrew J. , Hartman Angela , Bridges Janis P. , Jones Boyd R. , Mayhew Joe I. G.
Published: January 2017

Objective

To determine the effect of dorsal annulectomy and partial discectomy on the volume of the lumbosacral lateral intervertebral neurovascular foramina (intervertebral foramina) in canine cadavers during extension of the lumbosacral junction.

Study Design

Ex vivo experiment.

Sample Population: Lumbosacral specimens from 10 large breed dogs euthanatized for reasons unrelated to lumbosacral disease.

Methods

The lumbosacral specimens were clamped in a wooden jig and scanned using computed tomography (CT) with the lumbosacral junction in a neutral position and loaded in extension using a tensioning device. The 3‐dimensional volumes of the lumbosacral intervertebral neurovascular foramina were measured and the extent of any disc degeneration was determined from the CT data. A limited dorsal laminectomy of S1 and a dorsal LS annulectomy and partial discectomy were then performed. The lumbosacral specimens were remounted into the jig and loaded into extension at the same tension and were re‐scanned. Measurements of intervertebral foraminal volume were then repeated.

Results

The mean volume of the lumbosacral foramina (n = 20) was 381 mm3 in neutral (unloaded) positioning and 137 mm3 when loaded in extension. Following dorsal annulectomy, the mean volume was significantly reduced by a mean of 28% to 98 mm3 (P < .01). The foraminal volume was reduced in 19/20 lumbosacral foramen, with the post‐annulectomy volume ranging from 31% to 97% of the pre‐annulectomy volume (3%‐69% reduction).

Conclusions

This study suggests that a dorsal annulectomy with partial discectomy may induce further dynamic collapse of the lumbosacral articulation in the dog.
Joint stability after canine cranial cruciate ligament graft reconstruction varies among femoral fixation sites
Authors: Ho‐Eckart Louisa K. , Seki Masahiro , Luizza Lindsey , Kearney Michael T. , Lopez Mandi J.
Published: January 2017

Objective

To quantify stability in cranial cruciate ligament (CrCL) deficient canine stifles with hamstring grafts affixed at 3 femoral locations.

Study Design

Canine stifle motion study using a multi‐cohort, repeated measures design.

Sample Population

27 canine cadaver stifles.

Methods

Hamstring grafts (HG) were affixed at the gracilis‐semitendinosus insertion and on the lateral femur (1) proximal trochlear ridge (TR), (2) craniodistal to fabella (F), or (3) condyle center (CC). Total, cranial, and caudal tibial translation and total, medial, and lateral angular displacement, with and without translational load, were quantified with the CrCL intact, transected, and reconstructed. Angular displacement was quantified from points on the distal femur and proximal tibia. Graft strain was calculated from tissue displacement measured at joint angles of 30°, 60°, 90°, and 120°.

Results

Tibial translation was lowest in F constructs, which also achieved the least difference in tibial translation from intact stifles. Tibial translation was lower in intact stifles than in CrCL transected or reconstructed stifles. Less angular displacement of the proximal tibia was detected in the medial than in the lateral direction, and tibial displacement was lower in the cranial than the caudal direction. Angular displacement was lowest in the F treatment group. F constructs had the lowest graft strain at joint angles greater than 30°.

Conclusions

Femoral fixation of a canine hamstring graft craniodistal to the lateral fabella conferred the best joint stability and lowest graft strain in vitro. No fixation method restored joint stability of the intact CrCL.
Hypoxia and cellular metabolism in tumour pathophysiology
Authors: Parks Scott K. , Cormerais Yann , Pouysségur Jacques
Published: January 2017

Cancer cells are optimised for growth and survival via an ability to outcompete normal cells in their microenvironment. Many of these advantageous cellular adaptations are promoted by the pathophysiological hypoxia that arises in solid tumours due to incomplete vascularisation. Tumour cells are thus faced with the challenge of an increased need for nutrients to support the drive for proliferation in the face of a diminished extracellular supply. Among the many modifications occurring in tumour cells, hypoxia inducible factors (HIFs) act as essential drivers of key pro‐survival pathways via the promotion of numerous membrane and cytosolic proteins. Here we focus our attention on two areas: the role of amino acid uptake and the handling of metabolic acid (CO2/H+) production. We provide evidence for a number of hypoxia‐induced proteins that promote cellular anabolism and regulation of metabolic acid–base levels in tumour cells including amino‐acid transporters (LAT1), monocarboxylate transporters, and acid–base regulating carbonic anhydrases (CAs) and bicarbonate transporters (NBCs). Emphasis is placed on current work manipulating multiple CA isoforms and NBCs, which is at an interesting crossroads of gas physiology as they are regulated by hypoxia to contribute to the cellular handling of CO2 and pHi regulation. Our research combined with others indicates that targeting of HIF‐regulated membrane proteins in tumour cells will provide promising future anti‐cancer therapeutic approaches and we suggest strategies that could be potentially used to enhance these tactics.

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Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses
Authors: Roth Hanna , Magg Vera , Uch Fabian , Mutz Pascal , Klein Philipp , Haneke Katharina , Lohmann Volker , Bartenschlager Ralf , Fackler Oliver T. , Locker Nicolas , Stoecklin Georg , Ruggieri Alessia
Published: January 2017

As obligate parasites, viruses strictly depend on host cell translation for the production of new progeny, yet infected cells also synthesize antiviral proteins to limit virus infection. Modulation of host cell translation therefore represents a frequent strategy by which viruses optimize their replication and spread. Here we sought to define how host cell translation is regulated during infection of human cells with dengue virus (DENV) and Zika virus (ZIKV), two positive-strand RNA flaviviruses. Polysome profiling and analysis of
de novo
protein synthesis revealed that flavivirus infection causes potent repression of host cell translation, while synthesis of viral proteins remains efficient. Selective repression of host cell translation was mediated by the DENV polyprotein at the level of translation initiation. In addition, DENV and ZIKV infection suppressed host cell stress responses such as the formation of stress granules and phosphorylation of the translation initiation factor eIF2α (α subunit of eukaryotic initiation factor 2). Mechanistic analyses revealed that translation repression was uncoupled from the disruption of stress granule formation and eIF2α signaling. Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was essential for the efficient production of virus particles. Together, these results identify the uncoupling of translation suppression from the cellular stress responses as a conserved strategy by which flaviviruses ensure efficient replication in human cells.

IMPORTANCE
For efficient production of new progeny, viruses need to balance their dependency on the host cell translation machinery with potentially adverse effects of antiviral proteins produced by the infected cell. To achieve this, many viruses evolved mechanisms to manipulate host cell translation. Here we find that infection of human cells with two major human pathogens, dengue virus (DENV) and Zika virus (ZIKV), leads to the potent repression of host cell translation initiation, while the synthesis of viral protein remains unaffected. Unlike other RNA viruses, these flaviviruses concomitantly suppress host cell stress responses, thereby uncoupling translation suppression from stress granule formation. We identified that the p38-Mnk1 cascade regulating phosphorylation of eIF4E is a target of DENV infection and plays an important role in virus production. Our results define several molecular interfaces by which flaviviruses hijack host cell translation and interfere with stress responses to optimize the production of new virus particles.
A Unique
cis
-Encoded Small Noncoding RNA Is Regulating
Legionella pneumophila
Hfq Expression in a Life Cycle-Dependent Manner
Authors: Oliva Giulia , Sahr Tobias , Rolando Monica , Knoth Maike , Buchrieser Carmen
Published: January 2017

Legionella pneumophila
is an environmental bacterium that parasitizes protozoa, but it may also infect humans, thereby causing a severe pneumonia called Legionnaires’ disease. To cycle between the environment and a eukaryotic host,
L. pneumophila
is regulating the expression of virulence factors in a life cycle-dependent manner: replicating bacteria do not express virulence factors, whereas transmissive bacteria are highly motile and infective. Here we show that Hfq is an important regulator in this network. Hfq is highly expressed in transmissive bacteria but is expressed at very low levels in replicating bacteria. A
L. pneumophila hfq
deletion mutant exhibits reduced abilities to infect and multiply in
Acanthamoeba castellanii
at environmental temperatures. The life cycle-dependent regulation of Hfq expression depends on a unique
cis
-encoded small RNA named Anti-hfq that is transcribed antisense of the
hfq
transcript and overlaps its 5′ untranslated region. The Anti-hfq sRNA is highly expressed only in replicating
L. pneumophila
where it regulates
hfq
expression through binding to the complementary regions of the
hfq
transcripts. This results in reduced Hfq protein levels in exponentially growing cells. Both the small noncoding RNA (sRNA) and
hfq
mRNA are bound and stabilized by the Hfq protein, likely leading to the cleavage of the RNA duplex by the endoribonuclease RNase III. In contrast, after the switch to transmissive bacteria, the sRNA is not expressed, allowing now an efficient expression of the
hfq
gene and consequently Hfq. Our results place Hfq and its newly identified sRNA anti-
hfq
in the center of the regulatory network governing
L. pneumophila
differentiation from nonvirulent to virulent bacteria.

IMPORTANCE
The abilities of
L. pneumophila
to replicate intracellularly and to cause disease depend on its capacity to adapt to different extra- and intracellular environmental conditions. Therefore, a timely and fine-tuned expression of virulence factors and adaptation traits is crucial. Yet, the regulatory circuits governing the life cycle of
L. pneumophila
from replicating to virulent bacteria are only partly uncovered. Here we show that the life cycle-dependent regulation of the RNA chaperone Hfq relies on a small regulatory RNA encoded antisense to the
hfq
-encoding gene through a base pairing mechanism. Furthermore, Hfq regulates its own expression in an autoregulatory loop. The discovery of this RNA regulatory mechanism in
L. pneumophila
is an important step forward in the understanding of how the switch from inoffensive, replicating to highly virulent, transmissive
L. pneumophila
is regulated.
Effectiveness of a lumbopelvic monitor and feedback device to change postural behaviour: a protocol for the ELF cluster randomised controlled trial
Authors: Ribeiro Daniel Cury , Milosavljevic Stephan , Abbott J Haxby
Published: January 2017

Introduction

Low back pain (LBP) is the most common, costly and disabling musculoskeletal disorder worldwide, and is prevalent in healthcare workers. Posture is a modifiable risk factor for LBP shown to reduce the prevalence of LBP. Our feasibility research suggests that postural feedback might help healthcare workers avoid hazardous postures. The Effectiveness of Lumbopelvic Feedback (ELF) trial will investigate the extent to which postural monitor and feedback (PMF) can reduce exposure to hazardous posture associated with LBP.

Methods

This is a participant-blinded, randomised controlled trial with blocked cluster random allocation. Participants will include volunteer healthcare workers recruited from aged care institutions and hospitals. A postural monitoring and feedback device will monitor and record lumbopelvic forward bending posture, and provide audio feedback whenever the user sustains a lumbopelvic forward bending posture that exceeds predefined thresholds. The primary outcome measure will be postural behaviour (exceeding thresholds). Secondary outcome measures will be incidence of LBP, participant-reported disability and adherence. Following baseline assessment, we will randomly assign participants to 1 of 2 intervention arms: a feedback group and a no-feedback control group. We will compare between-group differences of changes in postural behaviour by using a repeated measures mixed-effect model analysis of covariance (ANCOVA) at 6 weeks. Postural behaviour baseline scores, work-related psychosocial factors and disability scores will be input as covariates into the statistical models. We will use logistic mixed model analysis and Cox's proportional hazards for assessing the effect of a PMF on LBP incidence between groups.

Discussion

Posture is a modifiable risk factor for low back disorders. Findings from the ELF trial will inform the design of future clinical trials assessing the effectiveness of wearable technology on minimising hazardous posture during daily living activities in patients with low back disorders.

Trial registration number

ACTRN12616000449437.
Accuracy of transbronchial biopsy as a rebiopsy method for patients with relapse of advanced non-small-cell lung cancer after systemic chemotherapy
Authors: Ishii Hidenobu , Azuma Koichi , Yamada Kazuhiko , Matsuo Norikazu , Nakamura Masayuki , Tokito Takaaki , Kinoshita Takashi , Hoshino Tomoaki
Published: January 2017

Introduction

Rebiopsy in patients with advanced non-small-cell lung cancer (NSCLC) resistant to systemic chemotherapy may yield information on the mechanisms of resistance and planning of subsequent treatment. Transbronchial biopsy (TBB) using a flexible bronchoscope has been commonly used for establishing the initial diagnosis of lung cancer. The aim of this study was to assess the accuracy and safety of TBB in patients with NSCLC relapse, and the factors affecting its diagnostic yield.

Methods

We retrospectively screened patients with advanced NSCLC who underwent TBB for rebiopsy after developing resistance to systemic chemotherapy at Kurume University Hospital between January 2012 and June 2016. A positive diagnostic result obtained by TBB was defined as malignancy determined on the basis of histological features that were adequate for mutational analysis or immunohistochemistry. Severe postprocedural complications were defined as those requiring invasive medical procedures or prolonged hospitalisation.

Results

109 patients were enrolled in this retrospective study. Adequate tumour samples were collected from 88 of these patients, giving a high diagnostic yield of 80.7%. The diagnostic yield of TBB was not associated with tumour mutational status, the previous treatment regimen, or efficacy of the previous treatment. There were no severe postprocedural complications such as pneumothorax or serious haemorrhage.

Conclusions

TBB is considered one of the safest and most useful procedures for rebiopsy of NSCLC that has relapsed after chemotherapy, regardless of patient background and treatment history.
Estimate of false-positive breast cancer diagnoses from accuracy studies: a systematic review
Authors: Segnan Nereo , Minozzi Silvia , Ponti Antonio , Bellisario Cristina , Balduzzi Sara , González-Lorenzo Marien , Gianola Silvia , Armaroli Paola
Published: January 2017

Background

False-positive histological diagnoses have the same consequences of overdiagnosis in terms of unnecessary treatment. The aim of this systematic review is to assess their frequency at needle core biopsy (CB) and/or surgical excision of the breast.

Methods

PubMed, Embase, Cochrane Library were systematically searched up to 30 October 2015. Eligibility criteria: cross-sectional studies assessing diagnostic accuracy of CB compared with surgical excision; studies assessing reproducibility of pathologists reading the same slides. Outcomes: false-positive rates; Misclassification of Benign as Malignant (MBM) histological diagnosis; K statistic. Independent reviewers extracted data and assessed quality using an adapted QUADAS-2 tool.

Results

Sixteen studies assessed CB false-positive rates. In 10 studies (41 989 screen-detected lesions), the range of false-positive rates was 0%–7.1%. Twenty-seven studies assessed pathologists' reproducibility. Studies with consecutive, random or stratified samples of all the specimens: at CB the MBM range was 0.25%–2.4% (K values 0.83–0.98); at surgical excision, it was 0.67%–1.2% (K values 0.86–0.94). Studies with enriched samples: the MBM range was 1.4%–6.2% (K values 0.57–0.86). Studies of cases selected for second opinion: the MBM range was 0.29%–12.2% (K values 0.48 and 0.50).

Conclusions

High heterogeneity of the included studies precluded formal pooling estimates. When considering studies of higher sample size or methodological quality, false-positive rates and MBM are around 1%. The impact of false-positive histological diagnoses of breast cancer on unnecessary treatment, as well as that of overdiagnosis, is not negligible and is of importance in clinical practice.
Computational design of three Cu-induced triangular pyrimidines based DNA motifs with improved conductivity
Authors: Lu Nan , Bu Yuxiang
Published: January 2017

Novel DNA triangular pyrimidine derivatives are designed by metal decoration through replacement of H by Cu in the Watson–Crick hydrogen bond region. The DFT method is used to examine the coordination of triangle-arranged Cu with three pyrimidines in nonplanar three-bladed turbine geometries. The Cu···Cu cuprophilic bonds are ascribed to the partially occupied d orbitals without direct molecular orbital (MO) interactions. Four-center bonds depend on Cu–N/O bonds, which are contributed by p orbitals of N/O atoms along or perpendicular to the bond axis. The activity of frontier MOs is modulated, leading to the decrease of gaps, ionization potentials (IPs), and electron affinities (EAs) desired for the improvement of conductivity. The hole trapping ability is assured by virtue of the spin density distributed on Cu. On average, the single electron density is located on π orbitals of three aromatic base rings. There is paramagnetic electron delocalization on the inner d orbitals of triangle region. The analysis of electron localization function ELF-π and electrostatic potential maps reveals that the outer strong π–π stacking interaction together with the inner d orbital channel enable effective transduction of electrical signals along the Cu–DNA nanowires. The 3Cu-induced triangular pyrimidines have important potential applications as structural motifs of molecular electronic devices.
Open access articles receive more citations in hybrid marine ecology journals
Authors: Clements Jeff C.
Published: January 2017

The accumulation of evidence that open access publishing can increase citation rates highlights one benefit of universal accessibility to scholarly works. However, studies investigating the effect of open access publishing on citations are typically conducted across a wide variety of journals and disciplines, introducing a number of potential issues and limiting their utility for specific disciplines. Here, I used three primary marine ecology journals with an open access option as a “microcosm” of scientific publishing to determine whether or not open access articles received more citations than non-open access articles during the same time frame, controlling for self-citations, article type, and journal impact factor. I also tested for the effects of time since publication and the number of authors. Citations were positively correlated with time since publication and differed across the three journals. In addition, open access articles received significantly more citations than non-open access articles. Self-citations increased with author number and were affected by a complex interaction between open access, journal, and time since publication. This study demonstrates that open access articles receive more citations in hybrid marine ecology journals, although the causal factors driving this trend are unknown.
The effective potential in nonconformal gauge theories
Authors: Brandt F. T. , Chishtie F. A. , McKeon D. G. C.
Published: January 2017

By using the renormalization group (RG) equation it has proved possible to sum logarithmic corrections to quantities that arise due to quantum effects in field theories. In particular, the effective potential [Formula: see text] in the Standard Model in the limit that there are no massive parameters in the classical action (the “conformal limit”) has been subject to this analysis, as has the effective potential in a scalar theory with a quartic self-coupling and in massless scalar electrodynamics. Having multiple coupling constants and/or mass parameters in the initial action complicates this analysis, as then several mass scales arise. We show how to address this problem by considering the effective potential in a Yukawa model when the scalar field has a tree-level mass term. In addition to summing logarithmic corrections by using the RG equation, we also consider the consequences of the condition [Formula: see text] where [Formula: see text] is the vacuum expectation value of the scalar. If [Formula: see text] is expanded in powers of logarithms that arise, then it proves possible to show that either [Formula: see text] is zero or that [Formula: see text] is independent of the scalar. (That is, either there is no spontaneous symmetry breaking or the vacuum expectation value is not determined by minimizing [Formula: see text] as [Formula: see text] is “flat”.)
Nonrelativistic anti-Snyder model and some applications
Authors: Ching C. L. , Yeo C. X. , Ng W. K.
Published: January 2017

In this paper, we examine the (2[Formula: see text]+[Formula: see text]1)-dimensional Dirac equation in a homogeneous magnetic field under the nonrelativistic anti-Snyder model which is relevant to doubly/deformed special relativity (DSR) since it exhibits an intrinsic upper bound of the momentum of free particles. After setting up the formalism, exact eigensolutions are derived in momentum space representation and they are expressed in terms of finite orthogonal Romanovski polynomials. There is a finite maximum number of allowable bound states [Formula: see text] due to the orthogonality of the polynomials and the maximum energy is truncated at [Formula: see text]. Similar to the minimal length case, the degeneracy of the Dirac–Landau levels in anti-Snyder model are modified and there are states that do not exist in the ordinary quantum mechanics limit [Formula: see text]. By taking [Formula: see text], we explore the motion of effective massless charged fermions in graphene-like material and obtained a maximum bound of deformed parameter [Formula: see text]. Furthermore, we consider the modified energy dispersion relations and its application in describing the behavior of neutrinos oscillation under modified commutation relations.
Reversible temperature-dependent differences in brown adipose tissue respiration during torpor in a mammalian hibernator
Authors: McFarlane Sarah V. , Mathers Katherine E. , Staples James F.
Published: January 2017

Although seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal and interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage. As predicted, maximal ETS enzyme activities of isolated BAT mitochondria did not differ between torpor and IBE. In contrast to this pattern, respiration rates of mitochondria isolated from torpid individuals were suppressed by ~60% compared with rates from IBE individuals when measured at 37°C. At 10°C, however, mitochondrial respiration rates tended to be greater in torpor than IBE. As a result, the temperature sensitivity (Q10) of mitochondrial respiration was significantly lower in torpor (~1.4) than IBE (~2.4), perhaps facilitating energy savings during entrance into torpor and thermogenesis at low body temperatures. Despite the observed differences in isolated mitochondria, norepinephrine-stimulated respiration rates of isolated BAT adipocytes did not differ between torpor and IBE, perhaps because the adipocyte isolation requires lengthy incubation at 37°C, potentially reversing any changes that occur in torpor. Such changes may include remodeling of BAT mitochondrial membrane phospholipids, which could change in situ enzyme activities and temperature sensitivities.