bluuebunny/crossref_metadata_2025 huggingface dataset:
Chest computed tomography imaging utility for radiographically occult rib fractures in elderly fall-injured patients
Authors: Singleton Jennifer M. , Bilello Leslie A. , Canham Louisa S. , Levenson Robin B. , Lopez Gregory J. , Tadiri Sarah P. , Shapiro Nathan I. , Rosen Carlo L.
Published: January 2019

BACKGROUND

Previous studies demonstrate an association between rib fractures and morbidity and mortality in trauma. This relationship in low-mechanism injuries, such as ground-level fall, is less clearly defined. Furthermore, computed tomography (CT) has increased sensitivity for rib fractures compared with chest x-ray (CXR); its utility in elderly fall patients is unknown. We sought to determine whether CT-diagnosed rib fractures in elderly fall patients with a normal CXR were associated with increased in-hospital resource utilization or mortality.

METHODS

Retrospective analysis of emergency department patients presenting over a 3-year period. Inclusion criteria: age, 65 years or older; chief complaint, including mechanical fall; and both CXR and CT obtained. We quantified rib fractures on CXR and CT and reported operating characteristics for both. Outcomes of interest included hospital admission/length of stay (LOS), intensive care unit (ICU) admission/LOS, endotracheal intubation, tube thoracostomy, locoregional anesthesia, pneumonia, in-hospital mortality.

RESULTS

We identified 330 patients, mean age was 84 years (±SD, 9.4 years); 269 (82%) of 330 were admitted. There were 96 (29%) patients with CT-diagnosed rib fracture, 56 (17%) by CT only. Compared with CT, CXR had a sensitivity of 40% (95% confidence interval, 30–50%) and specificity of 99% (95% confidence interval, 97–100%) for rib fracture. A median of two additional radiographically occult rib fractures were identified on CT. Despite an increased hospital admission rate (91% vs. 78%) p = 0.02, there was no difference between patients with and without radiographically occult (CT+ CXR−) rib fracture(s) for: median LOS (4; interquartile range (IQR) 2–7 vs 4, IQR 2–8); p = 0.92), ICU admission (28% vs. 27%) p = 0.62, median ICU LOS (2, IQR 1–8 vs 3, IQR 1–5) p = 0.54, or in-hospital mortality (10.3% vs. 7.3%) p = 0.45.

CONCLUSION

Among elderly fall patients, CT-identified rib fractures were associated with increased hospital admissions. However, there was no difference in procedural interventions, ICU admission, hospital/ICU LOS or mortality for patients with and without radiographically occult fractures.

LEVEL OF EVIDENCE

Diagnostic, level III.
A high-efficiency hydrocyclone designed by response surface methodology for acid hydrolysis residue recycling
Authors: Xu Yanxia , Tang Bo , Song Xingfu , Yu Jianguo
Published: January 2019

A high-efficiency hydrocyclone was designed by response surface methodology to evaluate the recycling of acid hydrolysis residues from titanium dioxide (TiO
2
) production as a study case. TiO
2
is an important product and the world's best white pigment. During its production from ilmenite (FeTiO
3
) by the sulfuric acid method, the incomplete reaction produces large amounts of residue, which also contain unreacted ilmenite. Large amounts of residue are generally accumulated without any treatment. Hydrocyclone use is regarded as a method for separating and recovering chemicals from process residues by which the unreacted components can be recycled efficiently. However, hydrocyclones designed by conventional procedures may have some limitations regarding classification sharpness. In this paper, numerical experiments and laboratory tests were performed to evaluate the classification sharpness of various hydrocyclone designs. Response surface methodology was used to optimize hydrocyclones with different structural configurations. Based on the response models, a designed hydrocyclone with a high sharpness of classification of particles was constructed. The sharpness of the newly designed hydrocyclone increased from 80.5% to 93.3%. The vortex finder separated approximately 89.9% of the fine particles in impurities, while 51.0% of TiO
2
was recycled by the spigot. The hydrocyclone proposed in this paper properly minimizes the risk of environmental pollution caused by TiO
2
production and provides a significant estimated cost savings.
Identification of copper (Cu) stress-responsive grapevine microRNAs and their target genes by high-throughput sequencing
Authors: Jiu Songtao , Leng Xiangpeng , Haider Muhammad Salman , Dong Tianyu , Guan Le , Xie Zhenqiang , Li Xiaopeng , Shangguan Lingfei , Fang Jinggui
Published: January 2019

MicroRNAs (miRNAs) are a class of single-stranded non-coding small RNAs (sRNAs) that are 20–24 nucleotides (nt) in length. Extensive studies have indicated that miRNAs play important roles in plant growth, development and stress responses. With more copper (Cu) and copper containing compounds used as bactericides and fungicides in plants, Cu stress has become one of the serious environmental problems that affect plant growth and development. In order to uncover the hidden response mechanisms of Cu stress, two small RNA libraries were constructed from Cu-treated and water-treated (Control) leaves of ‘Summer Black’ grapevine. Following high-throughput sequencing and filtering, a total of 158 known and 98 putative novel miRNAs were identified in the two libraries. Among these, 100 known and 47 novel miRNAs were identified as differentially expressed under Cu stress. Subsequently, the expression patterns of nine Cu-responsive miRNAs were validated by quantitative real-time PCR (qRT-PCR). There existed some consistency in expression levels of Cu-responsive miRNAs between high throughput sequencing and qRT-PCR assays. The targets prediction of miRNAs indicates that miRNA may regulate some transcription factors, including AP2, SBP, NAC, MYB and ARF during Cu stress. The target genes for two known and two novel miRNAs showed specific cleavage sites at the 10th and/or 11th nucleotide from the 5′-end of the miRNA corresponding to their miRNA complementary sequences. The findings will lay the foundation for exploring the role of the regulation of miRNAs in response to Cu stress and provide valuable gene information for breeding some Cu-tolerant grapevine cultivars.
Science podcasts: analysis of global production and output from 2004 to 2018
Authors: MacKenzie Lewis E.
Published: January 2019

Since 2004, podcasts have emerged as a decentralized medium for science communication to the global public. However, to date, there have been no large-scale quantitative studies of the production and dissemination of science podcasts. This study identified 952 English language science podcasts available between January and February 2018 and analysed online textual and visual data related to the podcasts and classified and noted key production parameters. It was found that the total number of science podcast series available grew linearly between 2004 and 2010, and then exponentially between 2010 and 2018. Sixty-five per cent of science podcast series were hosted by scientists and 77% were targeted to public audiences. Although a wide range of primarily single-subject science podcasts series were noted, 34% of science podcast series were not dedicated to a science subject. Compared to biology and physics, chemistry may be under-represented by science podcasts. Only 24% of science podcast series had any overt financial income. Sixty-two per cent of science podcast series were affiliated to an organization; producing a greater number of episodes (median = 24, average = 96) than independent science podcast series (median = 16, average = 48). This study provides the first ‘snapshot’ of how science podcasts are being used to communicate science to public audiences around the globe.
Epitaxial K
0.5
Na
0.5
NbO
3
thin films by aqueous chemical solution deposition
Authors: Pham Ky-Nam , Gaukås Nikolai Helth , Morozov Maxim , Tybell Thomas , Vullum Per Erik , Grande Tor , Einarsrud Mari-Ann
Published: January 2019

We report on an environmentally friendly and versatile aqueous chemical solution deposition route to epitaxial K
0.5
Na
0.5
NbO
3
(KNN) thin films. The route is based on the spin coating of an aqueous solution of soluble precursors on SrTiO
3
single crystal substrates followed by pyrolysis at 400°C and annealing at 800°C using rapid thermal processing. Strongly textured films with homogeneous thickness were obtained on three different crystallographic orientations of SrTiO
3
. Epitaxial films were obtained on (111) SrTiO
3
substrates, while films consisting of an epitaxial layer close to the substrate followed by an oriented polycrystalline layer were obtained on (100) and (110) SrTiO
3
substrates. A K
2
Nb
4
O
11
secondary phase was observed on the surface of the thin films due to the evaporation of alkali species, while the use of an NaCl/KCl flux reduced the amount of the secondary phase. Ferroelectric behaviour of the films was investigated by PFM, and almost no dependence on the film crystallographic orientation was observed. The permittivity and loss tangent of the films with the NaCl/KCl flux were 870 and 0.04 (100-orientation) and 2250 and 0.025 (110-orientation), respectively, at 1 kHz.
Effects of capsaicin-induced sensory denervation on early implant osseointegration in adult rats
Authors: Huang Bo , Ye Jun , Zeng Xiaohua , Gong Ping
Published: January 2019

The presence of nerve endings around implants is well-known, but the interaction between the peripheral nervous system and the osseointegration of implants has not been thoroughly elucidated to date. The purpose of this study was to test the effects of selective sensory denervation on early implant osseointegration. Forty male Sprague-Dawley rats were divided randomly into two groups, group A and group B, and they were treated with capsaicin and normal saline, respectively. One week later, titanium implants were placed in the bilateral femurs of the rats. Three and six weeks after implantation, histological examination, microcomputed tomography and biomechanical testing were performed to observe the effect of sensory denervation on implant osseointegration. At three weeks and six weeks, bone area, trabecular bone volume/total bone volume and bone density were significantly lower in group A than in group B. Similarly, the bone–implant contact rate, trabecular number and trabecular thickness were clearly lower in group A than in group B at three weeks. However, the trabecular separation spacing in group A was greater than that in group B at both time points. Biomechanical testing revealed that the implant-bone binding ability of group A was significantly lower than that in group B. The research demonstrated that sensory innervation played an important role in the formation of osseointegration. Selective-sensory denervation could reduce osseointegration and lower the binding force of the bone and the implant.
Mathematical modelling and application of frog choruses as an autonomous distributed communication system
Authors: Aihara Ikkyu , Kominami Daichi , Hirano Yasuharu , Murata Masayuki
Published: January 2019

Interactions using various sensory cues produce sophisticated behaviour in animal swarms, e.g. the foraging behaviour of ants and the flocking of birds and fish. Here, we investigate the behavioural mechanisms of frog choruses from the viewpoints of mathematical modelling and its application. Empirical data on male Japanese tree frogs demonstrate that (1) neighbouring male frogs avoid call overlaps with each other over a short time scale and (2) they collectively switch between the calling state and the silent state over a long time scale. To reproduce these features, we propose a mathematical model in which separate dynamical models spontaneously switch due to a stochastic process depending on the internal dynamics of respective frogs and also the interactions among the frogs. Next, the mathematical model is applied to the control of a wireless sensor network in which multiple sensor nodes send a data packet towards their neighbours so as to deliver the packet to a gateway node by multi-hop communication. Numerical simulation demonstrates that (1) neighbouring nodes can avoid a packet collision over a short time scale by alternating the timing of data transmission and (2) all the nodes collectively switch their states over a long time scale, establishing high network connectivity while reducing network power consumption. Consequently, this study highlights the unique dynamics of frog choruses over multiple time scales and also provides a novel bio-inspired technology that is applicable to the control of a wireless sensor network.
Prefrontal brain stimulation during food-related inhibition training: effects on food craving, food consumption and inhibitory control
Authors: Sedgmond Jemma , Lawrence Natalia S. , Verbruggen Frederick , Morrison Sinead , Chambers Christopher D. , Adams Rachel C.
Published: January 2019

Modulation of dorsolateral prefrontal cortex (DLPFC) activity using non-invasive brain stimulation has been shown to reduce food craving as well as food consumption. Using a preregistered design, we examined whether bilateral transcranial direct current stimulation (tDCS) of the DLPFC could reduce food craving and consumption in healthy participants when administered alongside the cognitive target of inhibitory control training. Participants (N= 172) received either active or sham tDCS (2 mA; anode F4, cathode F3) while completing a food-related Go/No-Go task. State food craving, ad-lib food consumption and response inhibition were evaluated. Compared with sham stimulation, we found no evidence for an effect of active tDCS on any of these outcome measures in a predominantly female sample. Our findings raise doubts about the effectiveness of single-session tDCS on food craving and consumption. Consideration of individual differences, improvements in tDCS protocols and multi-session testing are discussed.
Determination of the vapour pressure curves and vaporization enthalpies of hafnium alkoxides using thermogravimetric analysis
Authors: Wang Changhong , Yang Shenghai , Chen Yongming
Published: January 2019

In order to identify a volatile metallo-organic precursor for the deposition of hafnium oxide (HfO
2
) films for atomic layer deposition (ALD) applications, the evaporative properties of hafnium alkoxides (hafnium isopropoxide, hafnium
n
-propoxide and hafnium
n
-butoxide) were investigated using thermogravimetric analysis. These hafnium alkoxide samples were synthesized by the electrochemical method and characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance and inductively coupled plasma analysis techniques. The characterization results indicated that the products were 99.997% high-purity hafnium alkoxides and could meet the requirement of purity considering the usage of making HfO
2
gate oxide by ALD. Synthesized samples were subjected to a simultaneous thermogravimetric–differential thermal analysis unit at 10 K min
−1
in a dry nitrogen atmosphere flowing at 100 ml min
−1
. Benzoic acid was used to calculate a calibration constant, which could then be inserted into a modified Langmuir equation to calculate vapour pressure curves for hafnium isopropoxide and hafnium
n
-propoxide. Detailed vapour pressure data for the HfO
2
precursor hafnium alkoxides were determined. The vapour pressure curve of hafnium isopropoxide was constructed within the first stage, and calculated to be ln
p
= 31.157 (±0.200)−13130.57 (±56.50)/T. Hafnium
n
-propoxide and hafnium
n
-butoxide were simultaneously undergoing evaporation and decomposition, thus making calculations invalid.
Relationship between wear formation and large-particle motion in a pipe bend
Authors: Li Yi , Zhang Hebing , Lin Zhe , He Zhaohui , Xiang Jialiang , Su Xianghui
Published: January 2019

Fine and large particles flowing through a bend in a pipe move differently and therefore erode the pipe differently. This paper simulates solid–liquid two-phase flow containing large particles in a bend and analyses the relationship between the wear formation and particle motion. Wear experiments are carried out using 3-mm glass bead particles at a mass concentration of 1–15%. At the same time, the flow field and the motion of the granular system are obtained in computational fluid dynamics–discrete element method simulation. The wear formation mechanism is revealed by comparing experiments with numerical simulations. The wear rate of the wall surface increases with the mass concentration, while the marginal growth rate decreases as the mass concentration increases. As the mass concentration increases to a certain value, the degree of wear reaches a maximum and remains unchanged subsequently because of the formation of a particle barrier along the bend wall. The particles near the wall region will bounce forward because of the periodic disturbance flow around particles. The impact of mass bouncing particles causes the formation of the erosion ripple on the test sheet.
Effect of Fe(III) on the positive electrolyte for vanadium redox flow battery
Authors: Ding Muqing , Liu Tao , Zhang Yimin , Cai Zhenlei , Yang Yadong , Yuan Yizhong
Published: January 2019

It is important to study the effect of Fe(III) on the positive electrolyte, in order to provide some practical guidance for the preparation and use of vanadium electrolyte. The effect of Fe(III) on the thermal stability and electrochemical behaviour of the positive electrolyte for the vanadium redox flow battery (VRFB) was investigated. When the Fe(III) concentration was above 0.0196 mol l
−1
, the thermal stability of V(V) electrolyte was impaired, the diffusion coefficient of V(IV) species decreased from (2.06–3.33) × 10
−6
cm
2
s
−1
to (1.78–2.88) × 10
−6
cm
2
s
−1
, and the positive electrolyte exhibited a higher electrolyte resistance and a charge transfer resistance. Furthermore, Fe(III) could result in the side reaction and capacity fading, which would have a detrimental effect on battery application. With the increase of Fe(III), the collision probability of vanadium ions with Fe(III) and the competition with the redox reaction was aggravated, which would interfere with the electrode reaction, the diffusion of vanadium ions and the performance of VRFB. Therefore, this study provides some practical guidance that it is best to bring the impurity of Fe(III) below 0.0196 mol l
−1
during the preparation and use of vanadium electrolyte.
Orientation-invariance of individual differences in three face processing tasks
Authors: Meinhardt G. , Meinhardt-Injac B. , Persike M.
Published: January 2019

Numerous studies have reported impairments in perception and recognition, and, particularly, in part-integration of faces following picture-plane inversion. Whether these findings support the notion that inversion changes face processing qualitatively remains a topic of debate. To examine whether associations and dissociations of the human face processing ability depend on stimulus orientation, we measured face recognition with the Cambridge Face Memory Test (CFMT), along with experimental tests of face perception and selective attention to faces and non-face objects in a sample of 314 participants. Results showed strong inversion effects for all face-related tasks, and modest ones for non-face objects. Individual differences analysis revealed that the CFMT shared common variance with face perception and face-selective attention, however, independent of orientation. Regardless of whether predictor and criterion had same or different orientation, face recognition was best predicted by the same test battery. Principal component decomposition revealed a common factor for face recognition and face perception, a second common factor for face recognition and face-selective attention, and two unique factors. The patterns of factor loadings were nearly identical for upright and inverted presentation. These results indicate orientation-invariance of common variance in three domains of face processing. Since inversion impaired performance, but did not affect domain-related associations and dissociations, the findings suggest process-specific but orientation-general mechanisms. Specific limitations by constraints of individual differences analysis and test selection are discussed.
Integration of homogeneous structural region identification and rock mass quality classification
Authors: Chen Qingfa , Yin Tingchang
Published: January 2019

In rock engineering projects, professionals assess the overall rock mass qualities using a sole value. However, the true qualities of partial rock masses are incompatible with such a value. To address this problem, the idea of regionally classifying rock mass qualities is proposed and the associated procedure presented. To achieve this goal, the probabilistic and deterministic joints within the study area were determined, and a three-dimensional joint network model was created. Then, the three-dimensional joint network model was discretized into interlocking subdomains, and the modified blockiness index (

MB
i

) was used to finely identify the homogeneous structural regions, together with the
k
-means algorithm and the sum of squared errors (SSE). A synthetic model comprising homogeneous structural regions was developed and validated with respect to the extracted cross-sections. Next, an improved rock mass rating system (

RMR
mbi

) was introduced, and the viability of

RMR
mbi

was supported through a significant amount of theoretical cases and several real cases. Finally, visualization of regional

RMR
mbi

classification results was performed. Results show that: (i) the homogeneous structural regions are finely demarcated in three dimensions, and (ii) the proposed idea can overcome the problem of rock mass quality classification using the conventional approach often leading to ‘overgeneralization’.
Electron correlation in Li
+
, He, H
−
and the critical nuclear charge system
Z

C

: energies, densities and Coulomb holes
Authors: Baskerville Adam L. , King Andrew W. , Cox Hazel
Published: January 2019

This paper presents high-accuracy correlation energies, intracule densities and Coulomb hole(s) for the lithium cation, helium, hydride ion and the system with the critical nuclear charge,
Z

C

, for binding two electrons. The fully correlated (FC) wave function and the Hartree–Fock (HF) wave function are both determined using a Laguerre-based wave function. It is found that for the lithium cation and the helium atom a secondary Coulomb hole is present, in agreement with a previous literature finding, confirming a counterintuitive conclusion that electron correlation can act to bring distant electrons closer together. However, no evidence for a tertiary Coulomb hole is found. For the hydride anion and the system just prior to electron detachment only a single Coulomb hole is present and electron correlation decreases the probability of finding the electrons closer together at all radial distances. The emergence of a secondary Coulomb hole is investigated and found to occur between
Z
= 1.15 and
Z
= 1.20. The FC and HF energies and intracule densities (in atomic units) used to calculate the correlation energy and Coulomb hole, respectively, are accurate to at least the nano-scale for helium and the cation and at least the micro-scale for the anions.
Evolution of non-kin cooperation: social assortment by cooperative phenotype in guppies
Authors: Brask Josefine Bohr , Croft Darren P. , Edenbrow Mathew , James Richard , Bleakley Bronwyn H. , Ramnarine Indar W. , Heathcote Robert J. P. , Tyler Charles R. , Hamilton Patrick B. , Dabelsteen Torben , Darden Safi K.
Published: January 2019

Cooperation among non-kin constitutes a conundrum for evolutionary biology. Theory suggests that non-kin cooperation can evolve if individuals differ consistently in their cooperative phenotypes and assort socially by these, such that cooperative individuals interact predominantly with one another. However, our knowledge of the role of cooperative phenotypes in the social structuring of real-world animal populations is minimal. In this study, we investigated cooperative phenotypes and their link to social structure in wild Trinidadian guppies (
Poecilia reticulata
). We first investigated whether wild guppies are repeatable in their individual levels of cooperativeness (i.e. have cooperative phenotypes) and found evidence for this in seven out of eight populations, a result which was mostly driven by females. We then examined the social network structure of one of these populations where the expected fitness impact of cooperative contexts is relatively high, and found assortment by cooperativeness, but not by genetic relatedness. By contrast, and in accordance with our expectations, we did not find assortment by cooperativeness in a population where the expected fitness impact of cooperative contexts is lower. Our results provide empirical support for current theory and suggest that assortment by cooperativeness is important for the evolution and persistence of non-kin cooperation in real-world populations.
Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900
Authors: Dean Katharine R. , Krauer Fabienne , Schmid Boris V.
Published: January 2019

On 3 August 1900, bubonic plague (
Yersinia pestis
) broke out in Glasgow for the first time during the Third Pandemic. The local sanitary authorities rigorously tracked the spread of the disease and they found that nearly all of the 35 cases could be linked by contact with a previous case. Despite trapping hundreds of rats in the area, there was no evidence of a rat epizootic and the investigators speculated that the outbreak could be due to human-to-human transmission of bubonic plague. Here we use a likelihood-based method to reconstruct transmission trees for the outbreak. From the description of the outbreak and the reconstructed trees, we infer several epidemiological parameters. We found that the estimated mean serial interval was 7.4–9.2 days and the mean effective reproduction number dropped below 1 after implementation of control measures. We also found a high rate of secondary transmissions within households and observations of transmissions from individuals who were not terminally septicaemic. Our results provide important insights into the epidemiology of a bubonic plague outbreak during the Third Pandemic in Europe.
Ancestral diet transgenerationally influences offspring in a parent-of-origin and sex-specific manner
Authors: Emborski Carmen , Mikheyev Alexander S.
Published: January 2019

Parent-of-origin effects, whereby specific phenotypes are differentially inherited paternally or maternally, provide useful clues to better understand transgenerational effect transmission. Ancestral diet influences offspring phenotypes, including body composition and fitness. However, the specific role that mothers and fathers play in the transmission of altered phenotypes to male and female offspring remains unclear. We investigated the influence of the parent-of-origin's diet on adult progeny phenotypes and reproductive output for three generations in fruit flies (
Drosophila melanogaster
). Males and females reared on a control diet were exposed to the control diet or one of two altered (no- or high-) sugar treatment diets for a single generation. Flies from one of the two altered diet treatments were then mated to control flies in a full-factorial design to produce F
1
offspring and kept on control media for each following generation. We found parent-of-origin (triglyceride) and non-parent-of-origin (sugar) body composition effects, which were transgenerational and sex-specific. Additionally, we observed a negative correlation between intergenerational maternal reproductive output and triglyceride levels, suggesting that ancestral diet may affect fitness. This work demonstrates that ancestral diet can transmit altered phenotypes in a parent-of-origin and sex-specific manner and highlights that mechanisms regulating such transmission have been greatly overlooked.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Sexual selection, phenotypic plasticity and female reproductive output
Authors: Fox Rebecca J. , Fromhage Lutz , Jennions Michael D.
Published: January 2019

In a rapidly changing environment, does sexual selection on males elevate a population's reproductive output? If so, does phenotypic plasticity enhance or diminish any such effect? We outline two routes by which sexual selection can influence the reproductive output of a population: a genetic correlation between male sexual competitiveness and female lifetime reproductive success; and direct effects of males on females' breeding success. We then discuss how phenotypic plasticity of sexually selected male traits and/or female responses (e.g. plasticity in mate choice), as the environment changes, might influence how sexual selection affects a population's reproductive output. Two key points emerge. First, condition-dependent expression of male sexual traits makes it likely that sexual selection increases female fitnessifreproductively successful males disproportionately transfer genes that are under natural selection in both sexes, such as genes for foraging efficiency. Condition-dependence is a form of phenotypic plasticity if some of the variation in net resource acquisition and assimilation is attributable to the environment rather than solely genetic in origin. Second, the optimal allocation of resources into different condition-dependent traits depends on their marginal fitness gains. As male condition improves, this can therefore increase or, though rarely highlighted, actually decrease the expression of sexually selected traits. It is therefore crucial to understand how condition determines male allocation of resources to different sexually selected traits that vary in their immediate effects on female reproductive output (e.g. ornaments versus coercive behaviour). In addition, changes in the distribution of condition among males as the environment shifts could reduce phenotypic variance in certain male traits, thereby reducing the strength of sexual selection imposed by females. Studies of adaptive evolution under rapid environmental change should consider the possibility that phenotypic plasticity of sexually selected male traits, even if it elevates male fitness, could have a negative effect on female reproductive output, thereby increasing the risk of population extinction.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Sparse evidence for selection on phenotypic plasticity in response to temperature
Authors: Arnold Pieter A. , Nicotra Adrienne B. , Kruuk Loeske E. B.
Published: January 2019

Phenotypic plasticity is frequently assumed to be an adaptive mechanism by which organisms cope with rapid changes in their environment, such as shifts in temperature regimes owing to climate change. However, despite this adaptive assumption, the nature of selection on plasticity within populations is still poorly documented. Here, we performed a systematic review and meta-analysis of estimates of selection on thermal plasticity. Although there is a large literature on thermal plasticity, we found very few studies that estimated coefficients of selection on measures of plasticity. Those that did do not provide strong support for selection on plasticity, with the majority of estimates of directional selection on plasticity being weak and non-significant, and no evidence for selection on plasticity overall. Although further estimates are clearly needed before general conclusions can be drawn, at present there is not clear empirical support for any assumption that plasticity in response to temperature is under selection. We present a multivariate mixed model approach for robust estimation of selection on plasticity and demonstrate how it can be implemented. Finally, we highlight the need to consider the environments, traits and conditions under which plasticity is (or is not) likely to be under selection, if we are to understand phenotypic responses to rapid environmental change.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Effects of variations in adaptation potential on invasion speeds and species ranges
Authors: Méndez-Vera José , Raoul Gaël , Massol François , Loeuille Nicolas
Published: January 2019

Confronted with global changes and their potential impacts on biodiversity, an important question is to understand the ecological and evolutionary determinants of species geographical distributions. In order to understand how adaptation in heterogeneous environments constrains such distributions, we analyze how the potential of adaptation along an environmental cline affects the geographical distribution and propagation dynamics (invasion or extinction) of a single species. We re-analyse a model initially proposed by Kirkpatrick and Barton using propagation speed to assess whether species distribution is spatially limited or not.

We found that for big adaptation potentials, the species invades space following Fisher’s model, whereas for small adaptation potentials the propagation depends on the evolutionary challenge to overcome. We have explicit approximations for the propagation speeds in both cases. We discuss the utility of these propagation speeds as an eco-evolutionary index based on empirical studies.
Centering based on active diffusion in mouse oocytes is non-specific
Authors: Colin Alexandra , Razin Nitzan , Almonacid Maria , Ahmed Wylie , Betz Timo , Terret Marie-Emilie , Gov Nir S , Voituriez Raphaël , Gueroui Zoher , Verlhac Marie-Hélène
Published: January 2019

The mechanism for nucleus centering in mouse oocytes results from a gradient of actin-positive vesicles. By microinjecting oil droplets and fluorescent beads, we analyze the consequences of the gradient of activity on transport of exogenous tracer particles of different sizes. We also use optical tweezers to probe rheological properties of the cytoplasm. We find that the gradient activity induces a general centering force, akin to an effective pressure gradient, leading to centering of oil droplets with velocities comparable to nuclear ones. High temporal resolution measurements reveal that passive particles, larger than 1µm, experience the activity gradient by a biased diffusion towards the cell center. Unexpectedly, this general and size dependent mechanism is maintained in Meiosis I but contrasted by a further process that specifically off-centers the spindle. These antagonizing processes depend on myosin activity, thus we reconcile how the same molecular actors can have two opposite functions (centering versus off-centering).
Dual airway and alveolar contributions to adult lung homeostasis and carcinogenesis
Authors: Spella Magda , Lilis Ioannis , Pepe Mario A. , Chen Yuanyuan , Armaka Maria , Lamort Anne-Sophie , Zazara Dimitra E. , Roumelioti Fani , Vreka Malamati , Kanellakis Nikolaos I. , Wagner Darcy E. , Giannou Anastasios D. , Armenis Vasileios , Arendt Kristina A.M. , Klotz Laura V. , Toumpanakis Dimitrios , Karavana Vassiliki , Zakynthinos Spyros G. , Giopanou Ioanna , Marazioti Antonia , Aidinis Vassilis , Sotillo Rocio , Stathopoulos Georgios T.
Published: January 2019

Lung adenocarcinoma (LUAD) and chronic lung diseases caused by smoking and environmental noxious agents are the deadliest diseases worldwide, sharing a partially charted pathobiology of dysfunctional alveolar repair. Here we sought to identify the respiratory epithelial dynamics and molecular signatures participating in adult lung maintenance and chemical carcinogenesis. We employed novel mouse models of respiratory epithelial marking and ablation, a battery of pulmonary toxins and carcinogens, experimental protocols of carcinogen-induced LUAD, tobacco carcinogen-induced LUAD cell lines, and human transcriptomic data and identified a prominent involvement of airway molecular programs in alveolar maintenance and carcinogen-induced LUAD. The airway-specific transcriptomic signature was redistributed to the alveoli after toxic and carcinogenic insults and resulted in marked contributions of airway-labeled cells to injury-recovered alveoli and LUAD. Airway cells maintained Kras mutations and therefore possibly contributed to lung cancer initiation, while LUAD were spatially linked to neighboring airways. Transcriptomic profiling of carcinogen-induced murine and human LUAD revealed enrichment in airway signatures, while ablation of airway cells distorted alveolar structure and function and protected mice from LUAD development. Collectively, these results indicate that airway cells and/or transcriptomic signatures are essential for alveolar maintenance and LUAD development.
Potential hydrodynamic cytoplasmic transfer between mammalian cells: Cell-projection pumping
Authors: Zoellner Hans , Paknejad Navid , Cornwell James , Chami Belal , Romin Yevgeniy , Boyko Vitaly , Fujisawa Sho , Kelly Elizabeth , Lynch Garry W. , Rogers Glynn , Manova Katia , Moore Malcolm A.S.
Published: January 2019

We earlier reported cytoplasmic fluorescence exchange between cultured human fibroblasts (Fib) and malignant cells (MC). Others report similar transfer via either tunneling nanotubes (TNT) or shed membrane vesicles and this changes the phenotype of recipient cells. Our current time-lapse microscopy showed most exchange was from Fib into MC, with less in the reverse direction. Although TNT were seen, we were surprised transfer was not via TNT, but was instead via fine and often branching cell projections that defied direct visual resolution because of their size and rapid movement. Their structure was revealed nonetheless, by their organellar cargo and the grooves they formed indenting MC, while this was consistent with holotomography. Discrete, rapid and highly localized transfer events, evidenced against a role for shed vesicles. Transfer coincided with rapid retraction of the cell-projections, suggesting a hydrodynamic mechanism. Increased hydrodynamic pressure in retracting cell-projections normally returns cytoplasm to the cell body. We hypothesize ‘cell-projection pumping’ (CPP), where cytoplasm in retracting cell-projections partially equilibrates into adjacent recipient cells via micro-fusions that form temporary inter-cellular cytoplasmic continuities. We tested plausibility for CPP by combined mathematical modelling, comparison of predictions from the model with experimental results, and then computer simulations based on experimental data. The mathematical model predicted preferential CPP into cells with lower cell stiffness, expected from equilibration of pressure towards least resistance. Predictions from the model were satisfied when Fib were co-cultured with MC, and fluorescence exchange related with cell stiffness by atomic force microscopy. When transfer into 5000 simulated recipient MC or Fib was studied in computer simulations, inputting experimental cell stiffness and donor cell fluorescence values generated transfers to simulated recipient cells similar to those seen by experiment. We propose CPP as a potentially novel mechanism in mammalian inter-cellular cytoplasmic transfer and communication.

SIGNIFICANCE

Time-lapse observations of co-cultured cells led us to hypothesize what we believe to be a novel hydrodynamic mechanism transferring cytoplasm between cells. Similar transfer by other mechanisms markedly affects cell behavior. Combined mathematical modelling, satisfaction of predictions from the mathematical model in cell culture experiments, and separate computer simulations that generate outcomes similar to experimental observations, support our hypothesized mechanism.
Applying CRISPR-based genetic screens to identify drivers of tumor-cell sensitivity towards NK-cell attack
Authors: Klein Klara , Wang Tim , Lander Eric S. , Altfeld Marcus , Garcia-Beltran Wilfredo F.
Published: January 2019

Natural killer (NK) cells distinguish cancer cells from healthy cells using an array of germline-encoded receptors that interact with ligands expressed on target cells. A balance of inhibitory and activating signals transduced by these receptors regulate NK cell function to provide anti-tumor immunity while maintaining self-tolerance. However, knowledge of the spectrum of factors regulating NK-cell-mediated cytotoxicity, including the contribution of specific ligands and regulatory mechanisms for their expression on tumor cells, remains incomplete. Here, we apply a genome-wide loss-of-function screen in tumor cells using CRISPR/Cas9 technology to identify the factors that promote NK-cell cytotoxicity towards tumor cells. We established the drivers of tumor-cell sensitivity towards NK-cell attack (TuSeNKA) screening approach using the chronic myeloid leukemia (CML) cell line, K562. Interestingly, we identified B7H6, the ligand for the activating NK cell receptor NKp30, as the single factor whose loss resulted in increased resistance of K562 cells towards NK cells. Our study shows that combination of CRISPR-based genetic screens with NK-cell cytotoxicity assays is a valuable tool for identifying functionally relevant NK cell-tumor cell interactions, paving the way for further investigations that unravel the complexity of signals that promote NK-cell recognition of transformed cells and develop therapies that target these modes of tumor-cell killing.
Bone marrow stromal cells from a GDF5 origin produce zonal tendon-to-bone attachments following anterior cruciate ligament reconstruction
Authors: Hagiwara Yusuke , Dyrna Felix , Kuntz Andrew F , Adams Douglas J , Dyment Nathaniel A
Published: January 2019

Following anterior cruciate ligament (ACL) injury, the ligament is often reconstructed with a tendon graft passed through bone marrow tunnels. This procedure results in a staged repair response where cell death occurs in the tendon graft, the graft is repopulated by host cells outside the graft, and tendon-to-bone attachments form at the graft/bone interface. While this healing process is well appreciated, the biological mechanisms that regulate it including the cellular origin of the repair response is poorly understood. Embryonic progenitor cells expressing growth and differentiation factor 5 (GDF5) give rise to several mesenchymal tissues in the joint and epiphyses. Therefore, we hypothesized that cells from a GDF5 origin, even in the adult tissue, would give rise to cells that contribute to the stages of repair following ACL reconstruction. ACLs were reconstructed in Gdf5Cre;R26R-tdTomato lineage tracing mice to monitor the contribution of Gdf5Cre;tdTom+ cells to graft revitalization and examine the extent to which these cells are capable of creating mineralized attachments within the bone tunnels. Anterior-posterior drawer tests were used to establish the stability of the knee following the procedure and demonstrated 58% restoration in anterior-posterior stability. Following reconstruction, Gdf5Cre;tdTom+ cells within the bone marrow expanded by 135-fold compared to intact controls in response to the injury. These cells migrated to the tendon graft interface, repopulated regions of the graft, and initiated tendon-to-bone attachments. These cells continued to organize and mature the attachments yielding a zonal insertion site at 4 weeks with collagen fibers spanning across unmineralized and mineralized fibrocartilage and anchored to adjacent bone. The zonal attachment possessed organized tidemarks with concentrated alkaline phosphatase activity similar to normal tendon or ligament entheses. This study established that mesenchymal cells from a GDF5 origin contribute to the creation of zonal tendon-to-bone attachments within bone tunnels following ACL reconstruction. Future studies will target this cell population to modulate the repair response in order to better understand key biological mechanisms that regulate tendon-to-bone repair.
Summary statistic analyses do not correct confounding bias
Authors: Holmes John B. , Speed Doug , Balding David J.
Published: January 2019

LD SCore regression (LDSC) has become a popular approach to estimate confounding bias, heritability and genetic correlation using only genome wide association study (GWAS) test statistics. SumHer is a newly-introduced alternative with similar aims. We show using theory and simulations that both approaches fail to adequately account for confounding bias, even when the assumed heritability model is correct. Consequently, these methods may estimate heritability poorly if there was inadequate adjustment for confounding in the original GWAS analysis. We also show that choice of summary statistic for use in LDSC or SumHer can have a large impact on resulting inferences. Further, covariate adjustments in the original GWAS can alter the target of heritability estimation, which can be problematic when LDSC or SumHer is applied to test statistics from a meta-analysis of GWAS with different covariate adjustments.
Automated identification of Cell Types in Single Cell RNA Sequencing
Authors: Ma Feiyang , Pellegrini Matteo
Published: January 2019

Cell type identification is one of the major goals in single cell RNA sequencing (scRNA-seq). Current methods for assigning cell types typically involve the use of unsupervised clustering, the identification of signature genes in each cluster, followed by a manual lookup of these genes in the literature and databases to assign cell types. However, there are several limitations associated with these approaches, such as unwanted sources of variation that influence clustering and a lack of canonical markers for certain cell types. Here, we present ACTINN (Automated Cell Type Identification using Neural Networks), which employs a neural network with 3 hidden layers, trains on datasets with predefined cell types, and predicts cell types for other datasets based on the trained parameters. We trained the neural network on a mouse cell type atlas (Tabula Muris Atlas) and a human immune cell dataset, and used it to predict cell types for mouse leukocytes, human PBMCs and human T cell sub types. The results showed that our neural network is fast and accurate, and should therefore be a useful tool to complement existing scRNA-seq pipelines.

Author Summary

Single cell RNA sequencing (scRNA-seq) provides high resolution profiling of the transcriptomes of individual cells, which inevitably results in high volumes of data that require complex data processing pipelines. Usually, one of the first steps in the analysis of scRNA-seq is to assign individual cells to known cell types. To accomplish this, traditional methods first group the cells into different clusters, then find marker genes, and finally use these to manually assign cell types for each cluster. Thus these methods require prior knowledge of cell type canonical markers, and some level of subjectivity to make the cell type assignments. As a result, the process is often laborious and requires domain specific expertise, which is a barrier for inexperienced users. By contrast, our neural network ACTINN automatically learns the features for each predefined cell type and uses these features to predict cell types for individual cells. This approach is computationally efficient and requires no domain expertise of the tissues being studied. We believe ACTINN allows users to rapidly identify cell types in their datasets, thus rendering the analysis of their scRNA-seq datasets more efficient.