bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of In Situ Splitting Rib Harvesting Surgery for Orbital Deformity: Follow-Up
Authors: Sun Xiao-Ming , Ye Ling-Xiao , Jin Rong , Cheng Li-Ying , Zhang Ying , Zhang Yu-Guang , Zhang Lu
Published: June 2018

Background:

Our previous study indicated that in situ splitting rib harvesting surgery clinically reduced in related complications compared with the traditional surgical approach in the early stage, but there are few studies pay close attention to long-term recovery of donor area after rib harvesting. In this study, the authors conducted a follow-up study on recovery condition of donor and graft site of patients after in situ rib splitting grafting or simple whole rib grafting surgery.

Methods:

Between 2013 and 2016, 8 Chinese patients with orbital deformity were corrected using autogenous rib, of which 3 patients received conventional rib harvesting surgery, 3 patients received in situ splitting harvesting surgery, and 2 patients underwent both. In all patients, 3-dimensional computed tomography study of donor site and graft site were performed before and after operation. The ribs of donor site and graft site volume measurement were assessed using computed tomography 7 days and 12 months postoperation.

Results:

After 12 months operation, the integrity of rib arch recovered 94.1 ± 2.2% after in situ splitting rib harvesting, compared with 41.4 ± 5.0% after whole rib harvesting. The volume of grafted rib in situ splitting rib harvesting group reduced 69.8 ± 10.0% after 12 months operation compared with the volume after 1 week operation, and the reduced volume of ribs in whole rib harvesting group was 73.62 ± 9.5%.

Conclusion:

Rib regeneration occurred more quickly by in situ rib splitting harvesting approach compared with the traditional surgical approach.
The emerging role of digital health in monitoring and supporting people living with cancer and the consequences of its treatments
Authors: Harris Jenny , Cheevers Katy , Armes Jo
Published: June 2018

Purpose of review

As rising numbers of people are living with the long-term impact of cancer, digital health is playing an increasingly important role in the monitoring and support of survivors and their caregivers. This article reviews current evidence, practice and developments, and identifies emerging issues and opportunities.

Recent findings

Digital health innovations, primarily using internet or smartphone-enabled applications, have been successfully developed, particularly in the areas of symptom management, decision-making, survivorship and follow-up care and palliative care. The research is characterized by much developmental activity, and evidence is accruing for efficacy and effectiveness. Opportunities afforded by digital health include timelier and patient-centred evidence-based care, offering improved clinical outcomes and independence. Barriers to implementation include lack of patient and professional engagement, perceived burden, depersonalization and missed care.

There is much enthusiasm for the role of digital health in monitoring and providing support to cancer survivors, but further research is needed to establish clinical efficacy and understand the mechanisms for successful implementation in practice. The role of wearables, the internet of things and big data analytics is yet to be fully explored in supportive cancer care and may present new opportunities to enhance care and survivor experience.
Predictors of Postdischarge Surgical Recovery Following Laparoscopic Sacrocolpopexy: A Prospective Cohort Study
Authors: Heit Michael , Carpenter Janet S. , Chen Chen X. , Stewart Ryan , Hamner Jennifer , Rand Kevin L.
Published: June 2018

Objectives

Our aim was to identify sociodemographic/clinical, surgical, and psychosocial predictors of postdischarge surgical recovery after laparoscopic sacrocolpopexy.

Methods

Study participants (N = 171) with at least stage 2 pelvic organ prolapse completed a preoperative survey measuring hypothesized sociodemographic/clinical, surgical, and psychosocial recovery predictors followed by a postoperative survey at 4 time points (days 7, 14, 42, and 90) that included the Postdischarge Surgical Recovery 13 scale. One multivariate linear regression model was constructed for each time point to regress Postdischarge Surgical Recovery 13 scores on an a priori set of hypothesized predictors. All variables that had P < 0.1 were considered significant predictors of recovery because of the exploratory nature of this study and focus on model building rather than model testing.

Results

Predictors of recovery at 1 or more time points included the following: sociodemographic/clinical predictors: older age, higher body mass index, fewer comorbidities, and greater preoperative pain predicted greater recovery; surgical predictors: fewer perioperative complications and greater change in the leading edge of prolapse after surgery predicted greater recovery; psychosocial predictors: less endorsement of doctor's locus of control, greater endorsement of other's locus of control, and less sick role investment predicted greater recovery.

Conclusions

Identified sociodemographic/clinical, surgical, and psychosocial predictors should provide physicians with evidence-based guidance on recovery times for patients and family members. This knowledge is critical for informing future research to determine if these predictors are modifiable by changes to our narrative during the preoperative consultation visit. These efforts may reduce the postdischarge surgical recovery for patients with pelvic organ prolapse after laparoscopic sacrocolpopexy, accepting the unique demands on each individual's time.
Influence of Serotonin Transporter SLC6A4 Genotype on the Effect of Psychosocial Stress on Cognitive Performance: An Exploratory Pilot Study
Authors: Beversdorf David Q. , Carpenter Allen L. , Alexander Jessica K. , Jenkins Neil T. , Tilley Michael R. , White Catherine A. , Hillier Ashleigh J. , Smith Ryan M. , Gu Howard H.
Published: June 2018

Background and Objective:

Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43–base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams.

Methods:

In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants’ cognitive response to stress across genotypes.

Results:

A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition.

Conclusions:

Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.
Habitat partitioning during character displacement between the sexes
Authors: De Lisle Stephen P. , Paiva Samuel , Rowe Locke
Published: June 2018

Ecological differences between the sexes are often interpreted as evidence of within-species ecological character displacement (ECD), a hypothesis with almost no direct tests. Here, we experimentally test two predictions that are direct corollaries of ECD between the sexes, in a salamander. First, we find support for the prediction that each sex has a growth rate advantage in the aquatic microhabitat where it is most commonly found. Second, we test the prediction that selection for ECD in the breeding environment may affect partial migration out of this environment. We found that phenotype-dependent migration resulted in a shift in the phenotypic distribution across treatments, with the highest sexual dimorphism occurring among residents at high founding density, suggesting that migration and ECD can both be driven by competition. Our work illustrates how complex patterns of habitat partitioning evolve during ECD between the sexes and suggest ECD and partial migration can interact to effect both ecological dynamics and evolution of sexual dimorphism.
Effects of mistletoe (
Phoradendron villosum
) on California oaks
Authors: Koenig Walter D. , Knops Johannes M. H. , Carmen William J. , Pesendorfer Mario B. , Dickinson Janis L.
Published: June 2018

Mistletoes are a widespread group of plants often considered to be hemiparasitic, having detrimental effects on growth and survival of their hosts. We studied the effects of the Pacific mistletoe,
Phoradendron villosum
, a member of a largely autotrophic genus, on three species of deciduous California oaks. We found no effects of mistletoe presence on radial growth or survivorship and detected a significant positive relationship between mistletoe and acorn production. This latter result is potentially explained by the tendency of
P. villosum
to be present on larger trees growing in nitrogen-rich soils or, alternatively, by a preference for healthy, acorn-producing trees by birds that potentially disperse mistletoe. Our results indicate that the negative consequences of
Phoradendron
presence on their hosts are negligible—this species resembles an epiphyte more than a parasite—and outweighed by the important ecosystem services mistletoe provides.
On the lift-optimal aspect ratio of a revolving wing at low Reynolds number
Authors: Jardin T. , Colonius T.
Published: June 2018

Lentink & Dickinson (2009J. Exp. Biol.212, 2705–2719. (doi:10.1242/jeb.022269)) showed that rotational acceleration stabilized the leading-edge vortex on revolving, low aspect ratio (AR) wings and hypothesized that a Rossby number of around 3, which is achieved during each half-stroke for a variety of hovering insects, seeds and birds, represents a convergent high-lift solution across a range of scales in nature. Subsequent work has verified that, in particular, the Coriolis acceleration plays a key role in LEV stabilization. Implicit in these results is that there exists an optimal AR for wings revolving about their root, because it is otherwise unclear why, apart from possible morphological reasons, the convergent solution would not occur for an even lower Rossby number. We perform direct numerical simulations of the flow past revolving wings where we vary the AR and Rossby numbers independently by displacing the wing root from the axis of rotation. We show that the optimal lift coefficient represents a compromise between competing trends with competing time scales where the coefficient of lift increases monotonically with AR, holding Rossby number constant, but decreases monotonically with Rossby number, when holding AR constant. For wings revolving about their root, this favours wings of AR between 3 and 4.
The evolution of antibiotic resistance in a structured host population
Authors: Blanquart François , Lehtinen Sonja , Lipsitch Marc , Fraser Christophe
Published: June 2018

The evolution of antibiotic resistance in opportunistic pathogens such as
Streptococcus pneumoniae
,
Escherichia coli
or
Staphylococcus aureus
is a major public health problem, as infection with resistant strains leads to prolonged hospital stay and increased risk of death. Here, we develop a new model of the evolution of antibiotic resistance in a commensal bacterial population adapting to a heterogeneous host population composed of untreated and treated hosts, and structured in different host classes with different antibiotic use. Examples of host classes include age groups and geographic locations. Explicitly modelling the antibiotic treatment reveals that the emergence of a resistant strain is favoured by more frequent but shorter antibiotic courses, and by higher transmission rates. In addition, in a structured host population, localized transmission in host classes promotes both local adaptation of the bacterial population and the global maintenance of coexistence between sensitive and resistant strains. When transmission rates are heterogeneous across host classes, resistant strains evolve more readily in core groups of transmission. These findings have implications for the better management of antibiotic resistance: reducing the rate at which individuals receive antibiotics is more effective to reduce resistance than reducing the duration of treatment. Reducing the rate of treatment in a targeted class of the host population allows greater reduction in resistance, but determining which class to target is difficult in practice.
Contributions of metabolic and temporal costs to human gait selection
Authors: Summerside Erik M. , Kram Rodger , Ahmed Alaa A.
Published: June 2018

Humans naturally select several parameters within a gait that correspond with minimizing metabolic cost. Much less is understood about the role of metabolic cost in selecting between gaits. Here, we asked participants to decide between walking or running out and back to different gait specific markers. The distance of the walking marker was adjusted after each decision to identify relative distances where individuals switched gait preferences. We found that neither minimizing solely metabolic energy nor minimizing solely movement time could predict how the group decided between gaits. Of our twenty participants, six behaved in a way that tended towards minimizing metabolic energy, while eight favoured strategies that tended more towards minimizing movement time. The remaining six participants could not be explained by minimizing a single cost. We provide evidence that humans consider not just a single movement cost, but instead a weighted combination of these conflicting costs with their relative contributions varying across participants. Individuals who placed a higher relative value on time ran faster than individuals who placed a higher relative value on metabolic energy. Sensitivity to temporal costs also explained variability in an individual's preferred velocity as a function of increasing running distance. Interestingly, these differences in velocity both within and across participants were absent in walking, possibly due to a steeper metabolic cost of transport curve. We conclude that metabolic cost plays an essential, but not exclusive role in gait decisions.
Versatility of Turing patterns potentiates rapid evolution in tarsal attachment microstructures of stick and leaf insects (Phasmatodea)
Authors: Büscher Thies H. , Kryuchkov Mikhail , Katanaev Vladimir L. , Gorb Stanislav N.
Published: June 2018

In its evolution, the diverse group of stick and leaf insects (Phasmatodea) has undergone a rapid radiation. These insects evolved specialized structures to adhere to different surfaces typical for their specific ecological environments. The cuticle of their tarsal attachment pads (euplantulae) is known to possess a high diversity of attachment microstructures (AMS) which are suggested to reflect ecological specializations of different groups within phasmids. However, the origin of these microstructures and their developmental background remain largely unknown. Here, based on the detailed scanning electron microscopy study of pad surfaces, we present a theoretical approach to mathematically model an outstanding diversity of phasmid AMS using the reaction–diffusion model by Alan Turing. In general, this model explains pattern formation in nature. For the first time, we were able to identify eight principal patterns and simulate the transitions among these. In addition, intermediate transitional patterns were predicted by the model. The ease of transformation suggests a high adaptability of the microstructures that might explain the rapid evolution of pad characters. We additionally discuss the functional morphology of the different microstructures and their assumed advantages in the context of the ecological background of species.
Discrimination of volatiles in herbal formula Baizhu Shaoyao San before and after processing using needle trap device with multivariate data analysis
Authors: Xu Yangyang , Cai Hao , Cao Gang , Duan Yu , Pei Ke , Zhou Jia , Xie Li , Zhao Jiayu , Liu Jing , Wang Xiaoqi , Shen Lin
Published: June 2018

To characterize the chemical differences of volatile components between crude and processed Baizhu Shaoyao San (BSS), a classical Chinese herbal formula that is widely applied in the treatment of gastrointestinal diseases, we developed a gas chromatography–mass spectrometry-based needle trap device combined with multivariate data analysis to globally profile volatile components and rapidly identify differentiating chemical markers. Using a triple-bed needle packed with Carbopack X, DVB and Carboxen 1000 sorbents, we identified 121 and 123 compounds, respectively, in crude and processed BSS. According to the results of principal component analysis and orthogonal partial least-squares discriminant analysis, crude and processed BSS were successfully distinguished into two groups with good fitting and predicting parameters. Furthermore, 21 compounds were identified and adopted as potential markers that could be employed to quickly differentiate these two types of samples using S-PLOT and variable importance in projection analyses. The established method can be applied to explain the chemical transformation of Chinese medicine processing in BSS and further control the quality and understand the processing mechanism of Chinese herbal formulae. Besides, the triple-bed needle selected and optimized in this study can provide a valuable reference for other plant researches with similar components. Furthermore, the systematic research on compound identification and marker discrimination of the complex components in crude and processed BSS could work as an example for other similar studies, such as composition changes in one plant during different growth periods, botanical characters of different medicinal parts in same kind of medicinal herbs and quality identification of one species of medicinal herb from different regions.
Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by flufenamic acid
Authors: Saito G. , Velluto D. , Resmini M.
Published: June 2018

In this work, we report the synthesis of novel fluorescent molecules, based on 1,8-naphthalimide thio- and amino-derivatives, designed to display an OFF-ON and ON-OFF photoelectron transfer fluorescence switch upon interaction with a proton-donor drug. We have functionalized the new probes to allow easy formation of a covalent link to polymer matrices, for future applications as drug delivery sensors. We have investigated the fluorescent switch of the new probes using flufenamic acid (FA, pKa 3.65), a water insoluble, non-steroidal anti-inflammatory drug, as a model drug and proton source. The rapid interaction of the new probes with FA resulted in fluorescence enhancement or decrease and a large Stokes shift, all of which allowed the detection of the drug in the nanomolar range. The new 1,8-naphthalimide fluorescent dyes reported in this work are interesting tools for the detection and quantification of acidic drugs and biomolecules.
Development of low-cost non-contact structural health monitoring system for rotating machinery
Authors: Vanraj  , Singh Robin , Dhami S. S. , Pabla B. S.
Published: June 2018

Condition monitoring systems are increasingly being employed in industrial applications to improve the availability of equipment to increase the overall equipment efficiency. Condition monitoring of gearboxes, a key element of rotating machines, ensures to continuously reduce and eliminate costs, unscheduled downtime and unexpected breakdowns. This study demonstrates a low-cost microcontroller-based non-contact data acquisition system for condition monitoring of rotating machinery. Experimental validation of the proposed system was carried out by performing examination tests on a gearbox test rig. A user-friendly graphical user interface was also developed which facilitates users to perform signal processing in both real-time and offline mode. The proposed system can perform most of the functions available in complex, stand-alone vibration analysers. The use of a general-purpose PC and standard programing language makes the system simple, economical and adaptable to a variety of problems. The tests show the developed system can perform properly as proposed.
A new method of N to C sequential ligation using thioacid capture ligation and native chemical ligation
Authors: Hou Wen , Liu Lei , Zhang Xiaohong , Liu Chuanfa
Published: June 2018

Sequential peptide ligation strategy becomes more and more important in large protein or long peptides chemical synthesis due to the limited peptide/protein size obtained by solid phase synthesis of individual peptides or even one-step peptide ligation. Herein, we developed an alternative method which could perform the sequential peptide ligation of several segments from N to C direction based on the combined use of thioacid capture ligation and native chemical ligation. The sweet protein monellin was produced through this strategy on a scale of multi-milligrams.
Cracking the egg: the use of modern and fossil eggs for ecological, environmental and biological interpretation
Authors: Montanari Shaena
Published: June 2018

A myriad of extant and extinct vertebrates produce eggs. Eggs and eggshells provide a useful substrate for reconstructing environment, ecology and biology over a range of time scales from deep time to the present. In this review, methods for analysing and understanding records of diet, climate, environment and biology preserved in eggshells are presented. Topics covered include eggshell structure, assessing diagenesis, stable isotope geochemistry and morphological investigations of eggshell characteristics. This review emphasizes the use of eggshells in the modern and fossil record, as they allow for interpretation of characteristics of a wide variety of amniotes across geological history, uniquely informing environmental and ecological investigations.
A new terrestrial palaeoenvironmental record from the Bering Land Bridge and context for human dispersal
Authors: Wooller Matthew J. , Saulnier-Talbot Émilie , Potter Ben A. , Belmecheri Soumaya , Bigelow Nancy , Choy Kyungcheol , Cwynar Les C. , Davies Kimberley , Graham Russell W. , Kurek Joshua , Langdon Peter , Medeiros Andrew , Rawcliffe Ruth , Wang Yue , Williams John W.
Published: June 2018

Palaeoenvironmental records from the now-submerged Bering Land Bridge (BLB) covering the Last Glacial Maximum (LGM) to the present are needed to document changing environments and connections with the dispersal of humans into North America. Moreover, terrestrially based records of environmental changes are needed in close proximity to the re-establishment of circulation between Pacific and Atlantic Oceans following the end of the last glaciation to test palaeo-climate models for the high latitudes. We present the first terrestrial temperature and hydrologic reconstructions from the LGM to the present from the BLB's south-central margin. We find that the timing of the earliest unequivocal human dispersals into Alaska, based on archaeological evidence, corresponds with a shift to warmer/wetter conditions on the BLB between 14 700 and 13 500 years ago associated with the early Bølling/Allerød interstadial (BA). These environmental changes could have provided the impetus for eastward human dispersal at that time, from Western or central Beringia after a protracted human population standstill. Our data indicate substantial climate-induced environmental changes on the BLB since the LGM, which would potentially have had significant influences on megafaunal and human biogeography in the region.
Oxidation kinetics of YBaCo
4
O

7+
δ

and substituted oxygen carriers
Authors: Hou Limin , Yu Qingbo , Wang Kun , Qin Qin , Wei Mengqi , Yang Fan
Published: June 2018

In this paper, the relaxation kinetics of the oxidation process of the YBaCo
4
O

7+
δ

, Y
0.95
Ti
0.05
BaCo
4
O

7+
δ

and Y
0.5
Dy
0.5
BaCo
4
O

7+
δ

oxygen carriers is studied with isothermal reaction data. XRD analysis for fresh samples shows that all the samples have YBaCo
4
O

7+
δ

structure. Scanning electron microscopy images of samples show that the samples consist of porous agglomerates of primary particles. Isothermal TG experiments are conducted with temperatures of 290°C, 310°C, 330°C and 350°C, respectively. It is found that the Avrami-Eroféev model describes solid-phase changes in the oxygen absorption process adequately. The results show that the distributed activation energies of the oxidation process obtained by the Avrami-Eroféev model are 42.079 kJ mol
−1
, 42.944 kJ mol
−1
and 41.711 kJ mol
−1
for the YBaCo
4
O

7+
δ

, Y
0.95
Ti
0.05
BaCo
4
O

7+
δ

and Y
0.5
Dy
0.5
BaCo
4
O

7+
δ

oxygen carriers, respectively. The kinetic model was obtained to predict the oxygen carrier conversion of oxygen absorption for different time durations. The kinetic parameters obtained here are quite vital when this material is used in reactors.
Individual performance in team-based online games
Authors: Sapienza Anna , Zeng Yilei , Bessi Alessandro , Lerman Kristina , Ferrara Emilio
Published: June 2018

Complex real-world challenges are often solved through teamwork. Of special interest are ad hoc teams assembled to complete some task. Many popular multiplayer online battle arena (MOBA) video-games adopt this team formation strategy and thus provide a natural environment to study ad hoc teams. Our work examines data from a popular MOBA game, League of Legends, to understand the evolution of individual performance within ad hoc teams. Our analysis of player performance in successive matches of a gaming session demonstrates that a player’s success deteriorates over the course of the session, but this effect is mitigated by the player’s experience. We also find no significant long-term improvement in the individual performance of most players. Modelling the short-term performance dynamics allows us to accurately predict when players choose to continue to play or end the session. Our findings suggest possible directions for individualized incentives aimed at steering the player’s behaviour and improving team performance.
State-dependent risk-taking
Authors: Barclay Pat , Mishra Sandeep , Sparks Adam Maxwell
Published: June 2018

Who takes risks, and when? Therelative state modelproposes two non-independent selection pressures governing risk-taking: need-based and ability-based. The need-based account suggests that actors take risks when they cannot reach target states with low-risk options (consistent with risk-sensitivity theory). The ability-based account suggests that actors engage in risk-taking when they possess traits or abilities that increase the expected value of risk-taking (by increasing the probability of success, enhancing payoffs for success or buffering against failure). Adaptive risk-taking involves integrating both considerations. Risk-takers compute the expected value of risk-taking based on theirstate—the interaction of embodied capital relative to one's situation, to the same individual in other circumstances or to other individuals. We provide mathematical support for this dual pathway model, and show that it can predict who will take the most risks and when (e.g. when risk-taking will be performed by those in good, poor, intermediate or extreme state only). Results confirm and elaborate on the initial verbal model of state-dependent risk-taking: selection favours agents who calibrate risk-taking based on implicit computations of condition and/or competitive (dis)advantage, which in turn drives patterned individual differences in risk-taking behaviour.
Future effects of climate and land-use change on terrestrial vertebrate community diversity under different scenarios
Authors: Newbold Tim
Published: June 2018

Land-use and climate change are among the greatest threats facing biodiversity, but understanding their combined effects has been hampered by modelling and data limitations, resulting in part from the very different scales at which land-use and climate processes operate. I combine two different modelling paradigms to predict the separate and combined (additive) effects of climate and land-use change on terrestrial vertebrate communities under four different scenarios. I predict that climate-change effects are likely to become a major pressure on biodiversity in the coming decades, probably matching or exceeding the effects of land-use change by 2070. The combined effects of both pressures are predicted to lead to an average cumulative loss of 37.9% of species from vertebrate communities under ‘business as usual’ (uncertainty ranging from 15.7% to 54.2%). Areas that are predicted to experience the effects of both pressures are concentrated in tropical grasslands and savannahs. The results have important implications for the conservation of biodiversity in future, and for the ability of biodiversity to support important ecosystem functions, upon which humans rely.
Growth adaptation ofgndandsdhCB Escherichia colideletion strains diverges from a similar initial perturbation of the transcriptome
Authors: McCloskey Douglas , Xu Sibei , Sandberg Troy E. , Brunk Elizabeth , Hefner Ying , Szubin Richard , Beeken Lydia , Feist Adam M. , Palsson Bernhard O.
Published: June 2018

Adaptive laboratory evolution (ALE) has emerged as a new approach with which to pursue fundamental biological inquiries and, in particular, new insights into the systemic function of a gene product. TwoE. coliknockout strains were constructed: one that blocked the Pentose Phosphate Pathway (gnd KO) and one that decoupled the TCA cycle from electron transport (sdhCDABKO). Despite major perturbations in central metabolism, minimal growth rate changes were found in the two knockout strains. More surprisingly, many similarities were found in their initial transcriptomic states that could be traced to similarly perturbed metabolites despite the differences in the network location of the gene perturbations and concomitant rerouting of pathway fluxes around these perturbations. However, following ALE, distinct metabolomic and transcriptomic states were realized. These included divergent flux and gene expression profiles in thegndandsdhCDABKOs to overcome imbalances in NADPH production and nitrogen/sulfur assimilation, respectively, that were not obvious limitations of growth in the unevolved knockouts. Therefore, this work demonstrates that ALE provides a productive approach to reveal novel insights of gene function at a systems level that cannot be found by observing the fresh knockout alone.
Increased temperatures may safeguard the nutritional quality of crops under future elevated CO2 concentrations
Authors: Köhler Iris H. , Huber Steven C. , Bernacchi Carl J. , Baxter Ivan R.
Published: June 2018

Iron (Fe) and zinc (Zn) deficiencies are a global human health problem that may worsen by growth of crops at elevated atmospheric CO2 concentration (eCO2). However, climate change will also involve higher temperature, but it is unclear how the combined effect of eCO2 and higher temperature will affect the nutritional quality of food crops. To begin to address this question, we grew soybean (Glycine max) in a Temperature by Free-Air CO2 Enrichment (T-FACE) experiment in 2014 and 2015 under ambient (400 μmol mol−1) and elevated (600 μmol mol−1) CO2 concentration and under ambient and elevated temperatures (+2.7 °C day and +3.4 °C at night). In our study, eCO2 significantly decreased Fe concentration in soybean seeds in both seasons (−8.7% and −7.7%) and Zn concentration in one season (−8.9%) while higher temperature (at ambient CO2 concentration) had the opposite effect. The combination of eCO2 with elevated temperature generally restored seed Fe and Zn concentrations to levels obtained under ambient CO2 and temperature conditions, suggesting that the potential threat to human nutrition by increasing CO2 concentration may not be realized. In general, seed Fe concentration was negatively correlated with yield suggesting inherent limitations to increasing seed Fe. In addition, we confirm our previous report that the concentration of seed storage products and several minerals varies with node position at which the seeds developed. Overall, these results demonstrate the complexity of predicting climate change effects on food security when various environmental parameters change in an interactive manner.
Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage
Authors: Jochems Simon P. , Marcon Fernando , Carniel Beatriz F. , Holloway Mark , Mitsi Elena , Smith Emma , Gritzfeld Jenna F. , Solórzano Carla , Reiné Jesús , Pojar Sherin , Nikolaou Elissavet , German Esther L. , Hyder-Wright Angie , Hill Helen , Hales Caz , de Steenhuijsen Piters Wouter A.A , Bogaert Debby , Adler Hugh , Zaidi Seher , Connor Victoria , Rylance Jamie , Nakaya Helder I. , Ferreira Daniela M.
Published: June 2018

Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.
Pins & Needles: Towards Limb Disownership in Augmented Reality
Authors: Kannape Oliver A , Smith Ethan JT , Moseley Peter , Roy Mark P , Lenggenhager Bigna
Published: June 2018

The seemingly stable construct of our bodily self depends on the continued, successful integration of multisensory feedback about our body, rather than its purely physical composition. Accordingly, pathological disruption of such neural processing is linked to striking alterations of the bodily self, ranging from limb misidentification to disownership, and even the desire to amputate a healthy limb. While previous embodiment research has relied on experimental setups using supernumerary limbs in variants of the Rubber Hand Illusion, we here used Augmented Reality to directly manipulate the feeling of ownership for one’s own, biological limb. Using a Head-Mounted Display, participants received visual feedback about their own arm, from an embodied first-person perspective. In a series of three studies, in independent cohorts, we altered embodiment by providing visuotactile feedback that could be synchronous (control condition) or asynchronous (400ms delay, Real Hand Illusion). During the illusion, participants reported a significant decrease in ownership of their own limb, along with a lowered sense of agency. Supporting the right-parietal body network, we found an increased illusion strength for the left upper limb as well as a modulation of the feeling of ownership during anodal transcranial direct current stimulation. Extending previous research, these findings demonstrate that a controlled, visuotactile conflict about one’s own limb can be used to directly and systematically modulate ownership – without a proxy. This not only corroborates the malleability of body representation but questions its permanence. These findings warrant further exploration of combined VR and neuromodulation therapies for disorders of the bodily self.
Potent Cas9 inhibition in bacterial and human cells by new anti-CRISPR protein families
Authors: Lee Jooyoung , Mir Aamir , Edraki Alireza , Garcia Bianca , Amrani Nadia , Lou Hannah E. , Gainetdinov Ildar , Pawluk April , Ibraheim Raed , Gao Xin D. , Liu Pengpeng , Davidson Alan R. , Maxwell Karen L. , Sontheimer Erik J.
Published: June 2018

CRISPR-Cas systems are widely used for genome engineering technologies, and in their natural setting, they play crucial roles in bacterial and archaeal adaptive immunity, protecting against phages and other mobile genetic elements. Previously we discovered bacteriophage-encoded Cas9-specific anti-CRISPR (Acr) proteins that serve as countermeasures against host bacterial immunity by inactivating their CRISPR-Cas systems1. We hypothesized that the evolutionary advantages conferred by anti-CRISPRs would drive the widespread occurrence of these proteins in nature2–4. We have identified new anti-CRISPRs using the bioinformatic approach that successfully identified previous Acr proteins1 against Neisseria meningitidis Cas9 (NmeCas9). In this work we report two novel anti-CRISPR families in strains of Haemophilus parainfluenzae and Simonsiella muelleri, both of which harbor type II-C CRISPR-Cas systems5. We characterize the type II-C Cas9 orthologs from H. parainfluenzae and S. muelleri, show that the newly identified Acrs are able to inhibit these systems, and define important features of their inhibitory mechanisms. The S. muelleri Acr is the most potent NmeCas9 inhibitor identified to date. Although inhibition of NmeCas9 by anti-CRISPRs from H. parainfluenzae and S. muelleri reveals cross-species inhibitory activity, more distantly related type II-C Cas9s are not inhibited by these proteins. The specificities of anti-CRISPRs and divergent Cas9s appear to reflect co-evolution of their strategies to combat or evade each other. Finally, we validate these new anti-CRISPR proteins as potent off-switches for Cas9 genome engineering applications.
TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia inDrosophila
Authors: Lee Byoungchun , Barretto Elizabeth C. , Grewal Savraj S.
Published: June 2018

Animals often develop in conditions where environmental conditions such as food, oxygen and temperature fluctuate. The ability to adapt their metabolism to these fluctuations is important to ensure normal development and viability. In most animals, low oxygen (hypoxia) is deleterious, however some animals can alter their physiology to thrive under hypoxia. Here we show that TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia inDrosophila. We find that hypoxia rapidly suppresses TORC1 kinase signalling in Drosophila larvae via TSC-mediated inhibition of Rheb. We show that this hypoxia-mediated inhibition of TORC1 specifically in the larval fat body is essential for viable development to adulthood. Moreover, we find that these effects of TORC1 inhibition on hypoxia tolerance are mediated through remodeling of fat body lipid droplets and lipid storage. These studies identify the larval adipose tissue as a key hypoxia sensing tissue that coordinates whole-body development and survival to changes in environmental oxygen by modulating TORC1 and lipid storage.
High glucose-induced ubiquitylation of G6PD leads to the injury of podocyte
Authors: Wang Meng , Hu Ji , Yan Linling , Yang Yeping , He Min , Guo Shizhe , Wu Meng , Li Qin , Gong Wei , Yang Yang , Handy Diane E. , Lu Bin , Hao Chuanming , Wang Qinghua , Li Yiming , Hu Ronggui , Stanton Robert C. , Zhang Zhaoyun
Published: June 2018

Oxidative stress contributes substantially to podocyte injury in diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase is critical in maintaining NADPH, an important cofactor for antioxidant system. Here, we hypothesized that high glucose induces ubiquitylation and degradation of G6PD, which injures podocytes by reactive oxygen species (ROS) accumulation. We found that both G6PD protein expression and G6PD activity was decreased in kidneys of both diabetic patients and diabetic rodents. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD induced podocyte apoptosis. In G6PD deficient mice, podocyte apoptosis was also largely increased. High glucose had no effect on G6PD mRNA level but it caused decreased G6PD protein expression, which was mediated by the ubiquitin proteasome pathway. Furthermore, von Hippel−Lindau (VHL), an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on lysine residues 366/403. Our data suggest that high glucose induces ubiquitylation of G6PD by VHL, which leads to ROS accumulation and podocyte injury.
Polyploidy and elevation contribute to opposing latitudinal gradients in diversification and species richness in lady ferns (Athyriaceae)
Authors: Wei Ran , Ree Richard H. , Sundue Michael A. , Zhang Xian-Chun
Published: June 2018

In ferns, the temperate-tropical sister clades Athyrium and Diplazium present an opportunity to study a latitudinal contrast in diversification dynamics. We generated a taxonomically expanded molecular chronogram and used macroevolutionary models to analyze how diversification rates have changed through time, across lineages, and in concert with changes in elevation and ploidy. We tested a novel model of cladogenetic state-change in which polyploidy can arise as an infraspecific polymorphism, with diversification parameters distinct from those of pure diploids and polyploids. Both Athyrium and Diplazium accelerated their diversification near the Oligocene-Miocene transition. In Diplazium, the rate shift is older, with subsequent net diversification somewhat slower and suggestive of diversity-dependence. In Athyrium, diversification is faster and associated with higher elevations. In both clades, polyploids have the highest rate of net accumulation but lowest (negative) net diversification, while the converse is true for polymorphic species; diploids have low rates of both net accumulation and diversification. Diversification in Athyrium may have responded to ecological opportunities in expanding temperate habitats during the Neogene, especially in mountains, while the pattern in Diplazium suggests saturation in the tropics. Neopolyploids are generated rapidly, primarily through accelerated cladogenesis in polymorphic species, but are evolutionary dead ends.
Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position
Authors: Moreau Chloe , Caldarelli Paolo , Rocancourt Didier , Roussel Julian , Denans Nicolas , Pourquie Olivier , Gros Jerome
Published: June 2018

Limb position along the body is highly consistent within one species but very variable among vertebrates. Despite major advances in our understanding of limb patterning in three dimensions, how limbs reproducibly form along the anteroposterior axis remains largely unknown. Hox genes have long been suspected to control limb position, however supporting evidences are mostly correlative and their role in this process remains unclear. Here we show that Hox genes determine the avian forelimb position in a two-step process: first, their sequential collinear activation during gastrulation controls the relative position of their own successive expression domains along the body axis. Then, within these collinear domains, Hox genes differentially activate or repress the genetic cascade responsible for forelimb initiation. Furthermore, we provide evidences that changes in the timing of collinear Hox gene activation might underlie natural variation in forelimb position between different birds. Altogether our results which characterize the cellular and molecular mechanisms underlying the regulation and natural variation of forelimb position in avians, show a direct and early role for Hox genes in this process.
Measuring narrative engagement: The heart tells the story
Authors: Richardson Daniel C. , Griffin Nicole K. , Zaki Lara , Stephenson Auburn , Yan Jiachen , Curry Thomas , Noble Richard , Hogan John , Skipper Jeremy I. , Devlin Joseph T.
Published: June 2018

Stories play a fundamental role in human culture. They provide a mechanism for sharing cultural identity, imparting knowledge, revealing beliefs, reinforcing social bonds and providing entertainment that is central to all human societies. Here we investigated the extent to which the delivery medium of a story (audio or visual) affected conscious and subconscious engagement with the narrative. Although participants self-reported greater involvement for watching video relative to listening to auditory scenes, stronger physiological responses were recorded for auditory stories. Sensors placed at their wrists showed higher and more variable heart rates, greater electrodermal activity, and even higher body temperatures. We interpret these findings as physiological evidence that the stories were more cognitively and emotionally engaging when presented in an auditory format. This may be because listening to a story, rather than watching a video, is a more active process of co-creation, and that this imaginative process in the listener’s mind is detectable on the skin at their wrist.
An Equivariant Bayesian Convolutional Network predicts recombination hotspots and accurately resolves binding motifs
Authors: Brown Richard , Lunter Gerton
Published: June 2018

Motivation

Convolutional neural networks (CNNs) have been trememdously successful in many contexts, particularly where training data is abundant and signal-to-noise ratios are large. However, when predicting noisily observed biological phenotypes from DNA sequence, each training instance is only weakly informative, and the amount of training data is often fundamentally limited, emphasizing the need for methods that make optimal use of training data and any structure inherent in the model.

Results

Here we show how to combine equivariant networks, a general mathematical framework for handling exact symmetries in CNNs, with Bayesian dropout, a version of MC dropout suggested by a reinterpretation of dropout as a variational Bayesian approximation, to develop a model that exhibits exact reverse-complement symmetry and is more resistant to overtraining. We find that this model has increased power and generalizability, resulting in significantly better predictive accuracy compared to standard CNN implementations and state-of-art deep-learning-based motif finders. We use our network to predict recombination hotspots from sequence, and identify high-resolution binding motifs for the recombination-initiation protein PRDM9, which were recently validated by high-resolution assays. The network achieves a predictive accuracy comparable to that attainable by a direct assay of the H3K4me3 histone mark, a proxy for PRDM9 binding.

Availability

https://github.com/luntergroup/EquivariantNetworks

Contact

richard.brown@well.ox.ac.uk, gerton.lunter@well.ox.ac.uk

Supplementary information

Supplementary data are available at Bioinformatics online.