bluuebunny/crossref_metadata_2025 huggingface dataset:
High resolution (1 km) positive degree-day modelling of Greenland ice sheet surface mass balance, 1870–2012 using reanalysis data
Authors: WILTON DAVID J. , JOWETT AMY , HANNA EDWARD , BIGG GRANT R. , VAN DEN BROEKE MICHIEL R. , FETTWEIS XAVIER , HUYBRECHTS PHILIPPE
Published: December 2016

We show results from a positive degree-day (PDD) model of Greenland ice sheet (GrIS) surface mass balance (SMB), 1870–2012, forced with reanalysis data. The model includes an improved daily temperature parameterization as compared with a previous version and is run at 1 km rather than 5 km resolution. The improvements lead overall to higher SMB with the same forcing data. We also compare our model with results from two regional climate models (RCMs). While there is good qualitative agreement between our PDD model and the RCMs, it usually results in lower precipitation and lower runoff but approximately equivalent SMB: mean 1979–2012 SMB (± standard deviation), in Gt a−1, is 382 ± 78 in the PDD model, compared with 379 ± 101 and 425 ± 90 for the RCMs. Comparison with in situ SMB observations suggests that the RCMs may be more accurate than PDD at local level, in some areas, although the latter generally compares well. Dividing the GrIS into seven drainage basins we show that SMB has decreased sharply in all regions since 2000. Finally we show correlation between runoff close to two calving glaciers and either calving front retreat or calving flux, this being most noticeable from the mid-1990s.
Properties of latent variable network models
Authors: RASTELLI RICCARDO , FRIEL NIAL , RAFTERY ADRIAN E.
Published: December 2016

We derive properties of latent variable models for networks, a broad class of models that includes the widely used latent position models. We characterize several features of interest, with particular focus on the degree distribution, clustering coefficient, average path length, and degree correlations. We introduce the Gaussian latent position model, and derive analytic expressions and asymptotic approximations for its network properties. We pay particular attention to one special case, the Gaussian latent position model with random effects, and show that it can represent the heavy-tailed degree distributions, positive asymptotic clustering coefficients, and small-world behaviors that often occur in observed social networks. Finally, we illustrate the ability of the models to capture important features of real networks through several well-known datasets.
Neonatal milk supplementation in lambs has persistent effects on growth and metabolic function that differ by sex and gestational age
Authors: Berry Mary J. , Jaquiery Anne L. , Oliver Mark H. , Harding Jane E. , Bloomfield Frank H.
Published: December 2016

The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birthper seor the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose–insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVAP<0·01). In supplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem3)v. 69 (sem2) kg; PI, 48·0 (sem2·1)v. 43·7 (sem1·7) kg/m3; fasting insulin, 0·19 (sem0·02)v. 0·10 (sem0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem2)v. 70 (sem2) kg; PI, 44·4 (sem1·8)v. 48·2 (sem1·7) kg/m3; fasting insulin, 0·09 (sem0·02)v. 0·14 (sem0·02) ng/ml; all group×supplement interactionsP<0·05). Adult metabolic health may reflect both gestational age at birth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.
5-Hydroxyvitamin D concentration in paediatric cancer patients from Scotland: a prospective cohort study
Authors: Iniesta Raquel Revuelta , Paciarotti Ilenia , Davidson Isobel , McKenzie Jane M. , Brand Celia , Chin Richard F. M. , Brougham Mark F. H. , Wilson David C.
Published: December 2016

Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged <18 years diagnosed with, and treated for, cancer (patients) between August 2010 and January 2014 was performed, with control data from Scottish healthy children (controls). Clinical and nutritional data were collected at defined periods up to 24 months. 25(OH)D status was defined by the Royal College of Paediatrics and Child Health as inadequacy (<50 nmol/l: deficiency (<25 nmol/l), insufficiency (25–50 nmol/l)), sufficiency (51–75 nmol/l) and optimal (>75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9–8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8–9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33–50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0–46·5) to 45·0 (28·0–64·5) nmol/l. Older age at baseline (R −0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.
Acceptability and potential effectiveness of commercial portion control tools amongst people with obesity
Authors: Almiron-Roig Eva , Domínguez Angélica , Vaughan David , Solis-Trapala Ivonne , Jebb Susan A.
Published: December 2016

Exposure to large portion sizes is a risk factor for obesity. Specifically designed tableware may modulate how much is eaten and help with portion control. We examined the experience of using a guided crockery set (CS) and a calibrated serving spoon set (SS) by individuals trying to manage their weight. Twenty-nine obese adults who had completed 7–12 weeks of a community weight-loss programme were invited to use both tools for 2 weeks each, in a crossover design, with minimal health professional contact. A paper-based questionnaire was used to collect data on acceptance, perceived changes in portion size, frequency, and type of meal when the tool was used. Scores describing acceptance, ease of use and perceived effectiveness were derived from five-point Likert scales from which binary indicators (high/low) were analysed using logistic regression. Mean acceptance, ease of use and perceived effectiveness were moderate to high (3·7–4·4 points). Tool type did not have an impact on indicators of acceptance, ease of use and perceived effectiveness (P>0·32 for all comparisons); 55 % of participants used the CS on most days v. 21 % for the SS. The CS was used for all meals, whereas the SS was mostly used for evening meals. Self-selected portion sizes increased for vegetables and decreased for chips and potatoes with both tools. Participants rated both tools as equally acceptable, easy to use and with similar perceived effectiveness. Formal trials to evaluate the impact of such tools on weight control are warranted.
Reduced mobility but high survival: thermal tolerance and locomotor response of the specialist herbivore, Pareuchaetes insulata (Walker) (Lepidoptera: Erebidae), to low temperatures
Authors: Uyi O.O. , Zachariades C. , Marais E. , Hill M.P.
Published: December 2016

Disentangling the responses of insects to variations in their thermal environment is central to our understanding of the evolution of temperature-dependent performance in these species. Here, we report results of experiments examining the effects of high (upper lethal temperature = ULT) and low (lower lethal temperature = LLT) temperature and exposure time on the survival of larvae and adults of a multivoltine, nocturnal moth species, Pareuchaetes insulata, a biological control agent whose impact on an invasive weed, Chromolaena odorata has been variable in South Africa. The influence of temperature and acclimation on locomotion performance of the moth was also investigated. Temperature and duration of exposure significantly affected survival of both adults and larvae of P. insulata with more extreme temperatures and/or longer durations proving to be more lethal. Third instar larvae and adults are both freeze intolerant and had LT50 of −5.9 and −4.7°C, respectively, after a 2 h exposure. Although cold acclimation was beneficial to the nocturnal larvae, temperatures below 10°C significantly reduce their locomotion activities. The average daily minimum temperatures in the coldest months at three locations in South Africa are over 5°C lower than those of Fort Lauderdale, Florida, USA, where P. insulata was originally collected. Our results suggest that lethal high or low temperatures at short timescales are trivial in explaining the variable performance of P. insulata, but reduced locomotion at sub-lethal temperatures may be an important driver of the population dynamics of the biocontrol agent (especially in winter months) and may consequently explain the low population levels of the moth because of possible reduced feeding by larvae during night-time low temperatures.
Courtship and mating behaviour in the parasitoid waspCotesia urabae(Hymenoptera: Braconidae): mate location and the influence of competition and body size on male mating success
Authors: Avila G.A. , Withers T.M. , Holwell G.I.
Published: December 2016

Cotesia urabaeis a solitary larval endoparasitoid that was introduced into New Zealand in 2011 as a classical biological control agent againstUraba lugens. A detailed knowledge of its reproductive biology is required to optimize mass rearing efficiency. In this study, the courtship and mating behaviour ofC. urabaeis described and investigated from a series of experiments, conducted to understand the factors that influence male mating success.Cotesia urabaemales exhibited a high attraction to virgin females but not mated females, whereas females showed no attraction to either virgin or mated males. Male mating success was highest in the presence of a male competitor. Also, the time to mate was shorter and copulation duration was longer when a male competitor was present. Larger maleC. urabaehad greater mating success than smaller males when paired together with a single female. This knowledge can now be utilized to improve mass rearing methods ofC. urabaefor the future.
Haemosporida prevalence and diversity are similar in endangered wild whooping cranes (Grus americana) and sympatric sandhill cranes (Grus canadensis)
Authors: BERTRAM MIRANDA R. , HAMER GABRIEL L. , HARTUP BARRY K. , SNOWDEN KAREN F. , MEDEIROS MATTHEW C. , HAMER SARAH A.
Published: December 2016

The population growth of endangered whooping cranes (Grus americana) is not consistent with species recovery goals, and the impact of parasite infection on whooping crane populations is largely unknown. Disease ecology and epidemiology research of endangered species is often hindered by limited ability to conduct invasive sampling on the target taxa. Accordingly, we hypothesized that sandhill cranes (Grus canadensis) would be a useful surrogate species to investigate the health impacts of Haemosporida infection in whooping cranes. Our goal was to compare the prevalence and diversity of Haemosporida infection between whooping cranes and sandhill cranes. We detected an overall infection prevalence of 83·6% (n = 61) in whooping cranes and 59·6% (n = 47) and 63·6 (n = 22) in two sympatric sandhill crane populations captured in Texas. Prevalence was significantly lower in allopatric sandhill cranes captured in New Mexico (12·1%, n = 33). Haemoproteus antigonis was the most abundant haemoparasite in cranes, present in 57·4% of whooping cranes and 39·2% of sandhill cranes; Plasmodium and Leucocytozoon were present at significantly lower levels. The high prevalence of Haemosporida in whooping cranes and sympatric sandhill cranes, with shared parasite lineages between the two species, supports sandhill cranes as a surrogate species for understanding health threats to endangered whooping cranes.
Interventions to reduce the impact of unemployment and economic hardship on mental health in the general population: a systematic review
Authors: Moore T. H. M. , Kapur N. , Hawton K. , Richards A. , Metcalfe C. , Gunnell D.
Published: December 2016

Background

Job loss, debt and financial difficulties are associated with increased risk of mental illness and suicide in the general population. Interventions targeting people in debt or unemployed might help reduce these effects.

Method

We searched MEDLINE, Embase, The Cochrane Library, Web of Science, and PsycINFO (January 2016) for randomized controlled trials (RCTs) of interventions to reduce the effects of unemployment and debt on mental health in general population samples. We assessed papers for inclusion, extracted data and assessed risk of bias.

Results

Eleven RCTs (n= 5303 participants) met the inclusion criteria. All recruited participants were unemployed. Five RCTs assessed ‘job-club’ interventions, two cognitive behaviour therapy (CBT) and a single RCT assessed each of emotional competency training, expressive writing, guided imagery and debt advice. All studies were at high risk of bias. ‘Job club’ interventions led to improvements in levels of depression up to 2 years post-intervention; effects were strongest among those at increased risk of depression (improvements of up to 0.2–0.3s.d.in depression scores). There was mixed evidence for effectiveness of group CBT on symptoms of depression. An RCT of debt advice found no effect but had poor uptake. Single trials of three other interventions showed no evidence of benefit.

Conclusions

‘Job-club’ interventions may be effective in reducing depressive symptoms in unemployed people, particularly those at high risk of depression. Evidence for CBT-type interventions is mixed; further trials are needed. However the studies are old and at high risk of bias. Future intervention studies should follow CONSORT guidelines and address issues of poor uptake.
Clinical improvements following bilateral anterior capsulotomy in treatment-resistant depression
Authors: Subramanian L. , Bracht T. , Jenkins P. , Choppin S. , Linden D. E. J. , Phillips G. , Simpson B. A.
Published: December 2016

Background

The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD).

Method

This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery–Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samplesttest on the outcome measures to determine any statistically significant change in the group as a consequence of surgery.

Results

Patients improved on the clinical measure of depression after surgery by −21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred.

Conclusions

With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.
The ‘harder problem’ of the devil's fall is still a problem: a reply to Wood
Authors: BARNWELL MICHAEL
Published: December 2016

William Wood has importantly distinguished between a ‘hard problem’ and a ‘harder problem’ in explaining the devil's fall. He points out that previous attempts to explain Satan's sin have focused only on the former and cleverly argues that consumer preference theory, when applied to Anselm's account of Satan's sin, can solve the latter. In this article, I demonstrate that Wood's solution (i) undermines itself, (ii) fails to absolve God of the charge of being tyrannical, (iii) surreptitiously reintroduces the harder problem, and (iv) eventually collapses back into the initial hard problem. I conclude by suggesting why one might nonetheless be motivated to distinguish between the two problems and what this implies about a belief in the devil's fall.
The Running Fix on an Ellipsoid
Authors: Stuart Robin G.
Published: December 2016

The running fix or sight-run-sight fix is a classic problem in celestial navigation. Methods employed to obtain the fix traditionally involve advancing a Line of Position (LoP) taken at an earlier time and crossing it with one obtained later. Attempts to generalise the operation of advancing an LoP when the Earth's surface is represented by a plane to the case of the sphere have resulted in proposals that contain poorly constrained approximations or are otherwise fundamentally flawed. A simple rapidly-convergent iterative procedure to obtain a running fix is described that avoids the notion of advanced LoPs and is readily applicable to both the sphere and ellipsoid.
Closing the Courtroom: Press Restrictions and Criminal Trials in Late Nineteenth Century Germany
Authors: Hartston Barnet
Published: December 2016

In 1885 and 1886, two trials helped to precipitate a vigorous debate about when criminal proceedings should be closed to the public and when press reports on such cases should be restricted or banned altogether. First, the trial of the artist Gustav Graef for perjury and inappropriate relations with underage models featured sensationalized press reports that provoked a firestorm of public criticism. Soon afterward, press coverage of the trial of a Danish spy, Christian von Sarauw, revealed compromising details about German military planning and outraged government officials. The result was the proposal of a new law to limit public and press access to trials which posed a potential danger either to public decency or national security. Despite vigorous government efforts, this new legislation repeatedly stalled in the German Reichstag, in part because of concerns about protecting legal transparency and freedom of the press. The debates surrounding this law demonstrate the extent (and limits) to which liberal ideals such as legal transparency and freedom of the press had become embedded in Imperial German society and also the substantial power of the German Reichstag to obstruct the will of the government–even in making new laws deemed vital for national security.
Callous–unemotional behaviors in early childhood: Genetic and environmental contributions to stability and change
Authors: Flom Megan , Saudino Kimberly J.
Published: December 2016

Callous–unemotional (CU) behaviors demonstrate meaningful individual differences in early childhood, even in nonclinical samples with low mean levels of CU, but the factors underlying this variation have not been examined. This study investigated genetic and environmental contributions to individual differences and to sources of continuity and change in CU in toddler twins (145 monozygotic, 169 dizygotic) assessed at ages 2 and 3 years. CU, as assessed by the Child Behavior Checklist 1.5–5 (Achenbach & Rescorla, 2000), was moderately stable across age (r = .45, p < .0001). Longitudinal biometric analyses revealed genetic and nonshared environmental influences on CU at both ages, with no significant contribution from shared environmental factors. Stability from age 2 to 3 was due to genetic factors, whereas change was due to both genetic and nonshared environmental influences. This genetic and nonshared environmental change was substantial, suggesting malleability of CU in early childhood. Over 50% of the genetic influences and 100% of the nonshared environmental influences on CU at age 3 were independent of those that operated at age 2. Implications of novel sources of variance across age are discussed.
AN ILLUSTRATED GENERIC KEY AND UPDATED LIST OF THE GRASSES (POACEAE) OF BELIZE
Authors: Sylvester S. P.
Published: December 2016

A generic key to 81 genera representing 255 naturally occurring species known from Belize is presented using easily distinguished characters and including illustrations of many of the genera. An up-to-date list of the grasses of Belize is also given.
Diet in Saudi Arabia: findings from a nationally representative survey
Authors: Moradi-Lakeh Maziar , El Bcheraoui Charbel , Afshin Ashkan , Daoud Farah , AlMazroa Mohammad A , Al Saeedi Mohammad , Basulaiman Mohammed , Memish Ziad A , Al Rabeeah Abdullah A , Mokdad Ali H
Published: December 2016

Objective

No recent original studies on the pattern of diet are available for Saudi Arabia at the national level. The present study was performed to describe the consumption of foods and beverages by Saudi adults.

Design

The Saudi Health Interview Survey (SHIS) was conducted in 2013. Data were collected through interviews and anthropometric measurements were done. A diet history questionnaire was used to determine the amount of consumption for eighteen food or beverage items in a typical week.

Setting

The study was a household survey in all thirteen administrative regions of Saudi Arabia.

Subjects

Participants were 10 735 individuals aged 15 years or older.

Results

Mean daily consumption was 70·9 (se1·3) g for fruits, 111·1 (se2·0) g for vegetables, 11·6 (se0·3) g for dark fish, 13·8 (se0·3) g for other fish, 44·2 (se0·7) g for red meat, 4·8 (se0·2) g for processed meat, 10·9 (se0·3) g for nuts, 219·4 (se5·1) ml for milk and 115·5 (se2·6) ml for sugar-sweetened beverages. Dietary guideline recommendations were met by only 5·2 % of individuals for fruits, 7·5 % for vegetables, 31·4 % for nuts and 44·7 % for fish. The consumption of processed foods and sugar-sweetened beverages was high in young adults.

Conclusions

Only a small percentage of the Saudi population met the dietary recommendations. Programmes to improve dietary behaviours are urgently needed to reduce the current and future burden of disease. The promotion of healthy diets should target both the general population and specific high-risk groups. Regular assessments of dietary status are needed to monitor trends and inform interventions.
MODELS OF PT–WITH INTERNAL INDUCTION FOR TOTAL FORMULAE
Authors: CIEŚLIŃSKI CEZARY , ŁEŁYK MATEUSZ , WCISŁO BARTOSZ
Published: December 2016

We show that a typed compositional theory of positive truth with internal induction for total formulae (denoted by PTtot) is not semantically conservative over Peano arithmetic. In addition, we observe that the class of models of PA expandable to models of PTtotcontains every recursively saturated model of arithmetic. Our results point to a gap in the philosophical project of describing the use of the truth predicate in model-theoretic contexts.
Evidenzbasierte Psychokardiologie – oder was vom Typ-A-Verhalten übrigblieb
Authors: von Känel Roland
Published: December 2016

Zusammenfassung. Mit der Beschreibung des Typ-A-Verhaltens Ende der 1950er Jahre meinte man, einen psychosozialen Risikofaktor (PSRF) für das erhöhte Herzinfarktrisiko bei gestressten Managern gefunden zu haben. Aufgrund von Metaanalysen musste diese Vorstellung wieder verlassen werden. Heute weiss man, dass gerade Personen mit einem tieferen sozioökonomischen Status ein erhöhtes Infarktrisiko aufweisen und eine feindselige Einstellung gegenüber den Mitmenschen und eine hohe Ärgerbereitschaft die «kardiotoxischen» Komponenten der Typ-A-Persönlichkeit sind. Neben sozialen Faktoren und Persönlichkeitscharakteristika sind negative Emotionen und Erschöpfungszustände als weitere PSRF für kardiovaskuläre Krankheiten identifiziert worden. Genetische, verhaltensrelevante und pathophysiologische Mechanismen erklären diesen Zusammenhang. Die evidenzbasierte psychokardiologische Therapie kann in der psychosomatischen Grundversorgung und der kardialen Rehabilitation erfolgen und bezweckt eine Verbesserung der mentalen Gesundheit, des Funktionsniveaus im Alltag und der Krankheitsprognose.
TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial–mesenchymal transition
Authors: Amoroso Maria R , Matassa Danilo S , Agliarulo Ilenia , Avolio Rosario , Lu Haonan , Sisinni Lorenza , Lettini Giacomo , Gabra Hani , Landriscina Matteo , Esposito Franca
Published: December 2016

Ovarian cancer (OC) is the second leading cause of gynecological cancer death worldwide. Although the list of biomarkers is still growing, molecular mechanisms involved in OC development and progression remain elusive. We recently demonstrated that lower expression of the molecular chaperone TRAP1 in OC patients correlates with higher tumor grade and stage, and platinum resistance. Herein we show that TRAP1 is often deleted in high-grade serous OC patients (N=579), and that TRAP1 expression is correlated with the copy number, suggesting this could be one of the driving mechanisms for the loss of TRAP1 expression in OC. At molecular level, downregulation of TRAP1 associates with higher expression of p70S6K, a kinase frequently active in OC with emerging roles in cell migration and tumor metastasis. Indeed, TRAP1 silencing in different OC cells induces upregulation of p70S6K expression and activity, enhancement of cell motility and epithelial–mesenchymal transition (EMT). Consistently, in a large cohort of OC patients, TRAP1 expression is reduced in tumor metastases and directly correlates with the epithelial marker E-Cadherin, whereas it inversely correlates with the transcription factor Slug and the matrix metallopeptidases 2 and 9. Strikingly, pharmacological inhibition of p70S6K reverts the high motility phenotype of TRAP1 knock-down cells. However, although p70S6K inhibition or silencing reduces the expression of the transcription factors Snail and Slug, thus inducing upregulation of E-Cadherin expression, it is unable to revert EMT induced by TRAP1 silencing; furthermore, p70S6K did not show any significant correlation with EMT genes in patients, nor with overall survival or tumor stage, suggesting an independent and predominant role for TRAP1 in OC progression. Altogether, these results may provide novel approaches in OC with reduced TRAP1 expression, which could be resistant to therapeutic strategies based on the inhibition of the p70S6K pathway, with potential future intervention in OC invasion and metastasis.
Role of Fc–FcγR interactions in the antitumor activity of therapeutic antibodies
Authors: Barnhart Bryan C , Quigley Michael
Published: December 2016

The use of antibody therapy for cancer has steadily increased in recent years and has become standard treatment for numerous tumor types. It is now appreciated that the clinical activity of these antibodies relies upon their specific interactions with Fc receptors in addition to the well‐studied target‐binding region. The interactions mediated by antibody Fc domains can strongly affect the functional outcome of antibody therapy. The Fc portion of an antibody defines its interaction with numerous immune cells and has become an intense area of research as selecting the optimal Fc can greatly enhance the activity as well as mechanism of action of therapeutic antibodies. Recent advances in antibody engineering have enabled the development of antibodies that have altered Fc receptor interactions to take advantage of these findings. Engineering the Fc can fulfill diverse functions such as enhancing effector function for killing of tumor cells or depletion of unwanted immune subsets, enhancing agonist receptor signaling on particular immune cells or eliminating interaction with Fc receptors to avoid cellular depletion or toxicity in normal tissues. This review highlights important data and studies examining the role of Fc–Fc receptor interactions in therapeutic antibodies with a considerations for the future of engineered antibody therapy.
Profiling DNA damage response following mitotic perturbations
Authors: S. Pedersen Ronni , Karemore Gopal , Gudjonsson Thorkell , Rask Maj-Britt , Neumann Beate , Hériché Jean-Karim , Pepperkok Rainer , Ellenberg Jan , Gerlich Daniel W. , Lukas Jiri , Lukas Claudia
Published: December 2016

Genome integrity relies on precise coordination between DNA replication and chromosome segregation. Whereas replication stress attracted much attention, the consequences of mitotic perturbations for genome integrity are less understood. Here, we knockdown 47 validated mitotic regulators to show that a broad spectrum of mitotic errors correlates with increased DNA breakage in daughter cells. Unexpectedly, we find that only a subset of these correlations are functionally linked. We identify the genuine mitosis-born DNA damage events and sub-classify them according to penetrance of the observed phenotypes. To demonstrate the potential of this resource, we show that DNA breakage after cytokinesis failure is preceded by replication stress, which mounts during consecutive cell cycles and coincides with decreased proliferation. Together, our results provide a resource to gauge the magnitude and dynamics of DNA breakage associated with mitotic aberrations and suggest that replication stress might limit propagation of cells with abnormal karyotypes.
A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza
Authors: Smith Amber M. , Smith Amanda P.
Published: December 2016

Secondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.
Investigating the human Calcineurin Interaction Network using the πɸLxVP SLiM
Authors: Sheftic Sarah R. , Page Rebecca , Peti Wolfgang
Published: December 2016

Ser/thr phosphorylation is the primary reversible covalent modification of proteins in eukaryotes. As a consequence, it is the reciprocal actions of kinases and phosphatases that act as key molecular switches to fine tune cellular events. It has been well documented that ~400 human ser/thr kinases engage substrates via consensus phosphosite sequences. Strikingly, we know comparatively little about the mechanism by which ~40 human protein ser/thr phosphatases (PSPs) dephosphorylate ~15000 different substrates with high specificity. The identification of substrates of the essential PSP calcineurin (CN) has been exceptionally challenging and only a small fraction has been biochemically confirmed. It is now emerging that CN binds regulators and substrates via two short linear motifs (SLiMs), the well-studied PxIxIT SLiM and the LxVP SLiM, which remains controversial at the molecular level. Here we describe the crystal structure of CN in complex with its substrate NFATc1 and show that the LxVP SLiM is correctly defined as πɸLxVP. Bioinformatics studies using the πɸLxVP SLiM resulted in the identification of 567 potential CN substrates; a small subset was experimentally confirmed. This combined structural-bioinformatics approach provides a powerful method for dissecting the CN interaction network and for elucidating the role of CN in human health and disease.
Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells
Authors: Fani Somayeh , Kamalidehghan Behnam , Lo Kong Mun , Nigjeh Siamak Ebrahimi , Keong Yeap Swee , Dehghan Firouzeh , Soori Rahman , Abdulla Mahmood Ameen , Chow Kit May , Ali Hapipah Mohd , Hajiaghaalipour Fatemeh , Rouhollahi Elham , Hashim Najihah Mohd
Published: December 2016

In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.
Adsorption of phosphate in water using one-step synthesized zirconium-loaded reduced graphene oxide
Authors: Luo Xin , Wang Xiurong , Bao Shaopan , Liu Xiawei , Zhang Weicheng , Fang Tao
Published: December 2016

In this account, a one-step green hydrothermal method for zirconium-loaded reduced graphene oxide (RGO-Zr) adsorbent was developed in pure water. It is based on the formation of initially strong-coupling RGO-Zr nanocomposites followed by in situ reduction of GO to RGO during the hydrothermal treatment. The phosphate adsorption performance of the as-prepared nanocomposites was investigated in aqueous environment under various conditions. The characterization results of RGO-Zr nanocomposites showed that ZrO2 was successfully integrated onto the RGO sheets in amorphous. The data from equilibrium phosphate adsorption on RGO-Zr revealed that the adsorption kinetics followed a pseudo-second-order kinetic model, where the adsorption isotherm fitted the Langmuir isotherm model with a maximum adsorption capacity of 27.71 mg P/g at pH 5 and 298 K. The improved phosphate adsorption on RGO-Zr was caused by the dispersion of ZrO2 on the RGO surface. Furthermore, the phosphate adsorption was found insensitive to the increase in pH while it was sensitive to the increase in temperature. The coexisting anions of SO42−, F−, Cl−, NO3− and CO32− affected the phosphate adsorption in a different way. Results suggest that the present RGO-Zr adsorbent has the potential for controlling phosphorus pollution in water.
Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner
Authors: Coutaz Manuel , Hurrell Benjamin P. , Auderset Floriane , Wang Haiping , Siegert Stefanie , Eberl Gerard , Ho Ping-Chih , Radtke Freddy , Tacchini-Cottier Fabienne
Published: December 2016

Th17 cells play critical roles in host defense and autoimmunity. Emerging data support a role for Notch signaling in Th17 cell differentiation but whether it is a positive or negative regulator remains unclear. We report here that T cell-specific deletion of Notch receptors enhances Th17 cell differentiation in the gut, with a corresponding increase in IL-17 secretion. An increase in Th17 cell frequency was similarly observed following immunization of T cell specific Notch mutant mice with OVA/CFA. However, in this setting, Th17 cytokine secretion was impaired, and increased intracellular retention of IL-17 was observed. Intracellular IL-17 co-localized with the CD71 iron transporter in the draining lymph node of both control and Notch-deficient Th17 cells. Immunization induced CD71 surface expression in control, but not in Notch-deficient Th17 cells, revealing defective CD71 intracellular transport in absence of Notch signaling. Moreover, Notch receptor deficient Th17 cells had impaired mTORC2 activity. These data reveal a context-dependent impact of Notch on vesicular transport during high metabolic demand suggesting a role for Notch signaling in the bridging of T cell metabolic demands and effector functions. Collectively, our findings indicate a prominent regulatory role for Notch signaling in the fine-tuning of Th17 cell differentiation and effector function.
Adjacent tooth trauma in complicated mandibular third molar surgery: Risk degree classification and digital surgical simulation
Authors: Ye Zhou-Xi , Yang Chi , Ge Jing
Published: December 2016

Analysis of adjacent tooth resistance is essential in wisdom teeth extraction to prevent adjacent tooth trauma, however it lacks adequate attention nowadays. This study aims at suggesting special extraction methods based on adjacent tooth resistance analysis for prevention of adjacent tooth damage. In this study, 136 complicated mandibular third molars extracted using piezosurgery were reviewed and classified based on the adjacent teeth resistances shown in orthopantomogram (OPG) during their mesio-distal rotations: degree I refers to teeth with no adjacent teeth resistance; degree II refers to teeth with resistance released after mesial-half crown sectioning; degree III refers to teeth which still had resistance after mesial-half crown sectioning. With the use of surgical simulations using cone beam computerized tomography (CBCT) reconstruction, all teeth in degree I were designed to rotate mesio-distally; 86.36%(38/44) teeth in degree II were designed to rotate mesio-distally after mesio-half crown sectioning; 69.09%(36/55) teeth in degree III were designed to rotate bucco-lingually. All teeth were extracted successfully, and only one adjacent tooth was subluxated due to the incomplete bone removal. Our study suggested that in order to prevent adjacent teeth trauma, complete bone removal is of importance, and impacted teeth with higher adjacent teeth trauma risks should consider bucco-lingual rotations.
Simultaneous observation of free and defect-bound excitons in CH3NH3PbI3 using four-wave mixing spectroscopy
Authors: March Samuel A. , Clegg Charlotte , Riley Drew B. , Webber Daniel , Hill Ian G. , Hall Kimberley C.
Published: December 2016

Solar cells incorporating organic-inorganic perovskite, which may be fabricated using low-cost solution-based processing, have witnessed a dramatic rise in efficiencies yet their fundamental photophysical properties are not well understood. The exciton binding energy, central to the charge collection process, has been the subject of considerable controversy due to subtleties in extracting it from conventional linear spectroscopy techniques due to strong broadening tied to disorder. Here we report the simultaneous observation of free and defect-bound excitons in CH3NH3PbI3 films using four-wave mixing (FWM) spectroscopy. Due to the high sensitivity of FWM to excitons, tied to their longer coherence decay times than unbound electron- hole pairs, we show that the exciton resonance energies can be directly observed from the nonlinear optical spectra. Our results indicate low-temperature binding energies of 13 meV (29 meV) for the free (defect-bound) exciton, with the 16 meV localization energy for excitons attributed to binding to point defects. Our findings shed light on the wide range of binding energies (2–55 meV) reported in recent years.
Detecting sulphate aerosol geoengineering with different methods
Authors: Lo Y. T. Eunice , Charlton-Perez Andrew J. , Lott Fraser C. , Highwood Eleanor J.
Published: December 2016

Sulphate aerosol injection has been widely discussed as a possible way to engineer future climate. Monitoring it would require detecting its effects amidst internal variability and in the presence of other external forcings. We investigate how the use of different detection methods and filtering techniques affects the detectability of sulphate aerosol geoengineering in annual-mean global-mean near-surface air temperature. This is done by assuming a future scenario that injects 5 Tg yr−1 of sulphur dioxide into the stratosphere and cross-comparing simulations from 5 climate models. 64% of the studied comparisons would require 25 years or more for detection when no filter and the multi-variate method that has been extensively used for attributing climate change are used, while 66% of the same comparisons would require fewer than 10 years for detection using a trend-based filter. This highlights the high sensitivity of sulphate aerosol geoengineering detectability to the choice of filter. With the same trend-based filter but a non-stationary method, 80% of the comparisons would require fewer than 10 years for detection. This does not imply sulphate aerosol geoengineering should be deployed, but suggests that both detection methods could be used for monitoring geoengineering in global, annual mean temperature should it be needed.
The genome of Rhizobiales bacteria in predatory ants reveals urease gene functions but no genes for nitrogen fixation
Authors: Neuvonen Minna-Maria , Tamarit Daniel , Näslund Kristina , Liebig Juergen , Feldhaar Heike , Moran Nancy A. , Guy Lionel , Andersson Siv G. E.
Published: December 2016

Gut-associated microbiota of ants include Rhizobiales bacteria with affiliation to the genus Bartonella. These bacteria may enable the ants to fix atmospheric nitrogen, but no genomes have been sequenced yet to test the hypothesis. Sequence reads from a member of the Rhizobiales were identified in the data collected in a genome project of the ant Harpegnathos saltator. We present an analysis of the closed 1.86 Mb genome of the ant-associated bacterium, for which we suggest the species name Candidatus Tokpelaia hoelldoblerii. A phylogenetic analysis reveals a relationship to Bartonella and Brucella, which infect mammals. Novel gene acquisitions include a gene for a putative extracellular protein of more than 6,000 amino acids secreted by the type I secretion system, which may be involved in attachment to the gut epithelium. No genes for nitrogen fixation could be identified, but genes for a multi-subunit urease protein complex are present in the genome. The urease genes are also present in Brucella, which has a fecal-oral transmission pathway, but not in Bartonella, which use blood-borne transmission pathways. We hypothesize that the gain and loss of the urease function is related to transmission strategies and lifestyle changes in the host-associated members of the Rhizobiales.
Leisure-Time Physical Activity and Academic Performance: Cross-Lagged Associations from Adolescence to Young Adulthood
Authors: Aaltonen Sari , Latvala Antti , Rose Richard J. , Kujala Urho M. , Kaprio Jaakko , Silventoinen Karri
Published: December 2016

Physical activity and academic performance are positively associated, but the direction of the association is poorly understood. This longitudinal study examined the direction and magnitude of the associations between leisure-time physical activity and academic performance throughout adolescence and young adulthood. The participants were Finnish twins (from 2,859 to 4,190 individuals/study wave) and their families. In a cross-lagged path model, higher academic performance at ages 12, 14 and 17 predicted higher leisure-time physical activity at subsequent time-points (standardized path coefficient at age 14: 0.07 (p < 0.001), age 17: 0.12 (p < 0.001) and age 24: 0.06 (p < 0.05)), whereas physical activity did not predict future academic performance. A cross-lagged model of co-twin differences suggested that academic performance and subsequent physical activity were not associated due to the environmental factors shared by co-twins. Our findings suggest that better academic performance in adolescence modestly predicts more frequent leisure-time physical activity in late adolescence and young adulthood.
A window into the brain mechanisms associated with noise sensitivity
Authors: Kliuchko Marina , Heinonen-Guzejev Marja , Vuust Peter , Tervaniemi Mari , Brattico Elvira
Published: December 2016

Noise sensitive individuals are more likely to experience negative emotions from unwanted sounds and they show greater susceptibility to adverse effects of noise on health. Noise sensitivity does not originate from dysfunctions of the peripheral auditory system, and it is thus far unknown whether and how it relates to abnormalities of auditory processing in the central nervous system. We conducted a combined electroencephalography and magnetoencephalography (M/EEG) study to measure neural sound feature processing in the central auditory system in relation to the individual noise sensitivity. Our results show that high noise sensitivity is associated with altered sound feature encoding and attenuated discrimination of sound noisiness in the auditory cortex. This finding makes a step towards objective measures of noise sensitivity instead of self-evaluation questionnaires and the development of strategies to prevent negative effects of noise on the susceptible population.