bluuebunny/crossref_metadata_2025 huggingface dataset:
Iatrogenic Conchal Defect Secondary to Auricular Cartilage Graft
Authors: Mundra Leela S. , AlQattan Husain T. , Janette Meghan G. , Patete Carissa , Thaller Seth R.
Published: February 2018

Background:

Cleft lip and palate are the most common craniofacial congenital malformations. Timing of the nasal repair remains somewhat controversial. Some authors perform a combined nasal and lip repair in infancy while others advocate for a staged repair with the nasal component occurring later in childhood. Frequently, secondary repair is needed to address residual nasal deformities in early adulthood. Conchal cartilage has become increasingly popular as a source of cartilage for secondary reconstruction. Donor site morbidities include hematoma formation, scar formation, and wound healing complications. To the best of the authors’ knowledge, there is 1 previous report of a full through—and—through conchal defect as a complication of auricular cartilage graft harvesting. The authors report an infrequently described iatrogenic conchal defect due to cartilage harvesting managed with a single-stage reconstruction using bookend flaps.

Methods:

A 19-year-old female with a history of unilateral cleft lip and palate repair underwent secondary rhinoplasty using conchal cartilage. A bolster dressing was applied to the conchal harvest site. The patient was unable to attend her postoperative clinic visit and was eventually seen 2 months postoperatively with the bolster still in place. A full-thickness conchal defect was present when the bolster was removed.

Results:

A pressure dressing such as a bolster is commonly used to prevent hematoma formation after conchal cartilage graft harvesting. This is routinely removed during the initial postoperative visit. Prolonged placement can result in donor site complications such as a full-thickness conchal defect.

Conclusion:

A functional and aesthetic reconstruction of a full-thickness iatrogenic conchal defect was achieved with excellent results using a local posterior flap, and 2 anteriorly based bookend flaps for closure. To the best of the authors’ knowledge, this report is the first to describe a single-stage reconstruction of an iatrogenic defect in the concha as a complication of conchal cartilage harvesting.
Risk Assessment of Isolated Single-Wall Orbit Fractures and Eye Injury
Authors: Thurston Todd E. , Jackson Anee S. , Nazir Naiman , Crowe Danielle , Andrews Brian T.
Published: February 2018

Introduction:

Ideally, all patients with isolated orbit fracture would undergo ophthalmologic evaluation before surgical intervention to rule out concomitant globe injury and possible vision loss. Unfortunately, not all institutions are capable of providing the evaluation before surgery. The authors hypothesize that the anatomic location of a single-wall orbit isolated orbit fracture can help predict the likelihood of ocular injury and thus identify high-risk patients who mandate ophthalmologic evaluation before surgical repair.

Methods:

A retrospective chart review was performed at a tertiary academic medical center using the institutional trauma registry for maxillofacial trauma. All subjects with an isolated single-wall orbit fracture were included in this study. Statistical analysis was performed using a Fisher exact test.

Results:

Two hundred seventy-nine subjects with orbit fractures were identified for inclusion in this study. Forty-one of the 279 (14.7%) subjects had isolated single-wall orbit fractures. Isolated single-wall fractures included orbit floor = 19 of 41 (46.3%), medial wall = 15 of 41 (36.6%), lateral wall = 4 of 41 (9.8%), and orbit roof = 3 of 41 (7.3%). Concomitant ocular injury (13 of 41, 31.8%) was associated with isolated orbit wall fractures as follows: orbit floor = 4 of 19 (21.1%), medial wall = 6 of 15 (40%), lateral wall = 2 of 4 (50%), and orbit roof = 1 of 3 (33.3%). A Fisher exact test demonstrated that there was no statistically significant association between individual isolated wall fractures and ocular injury (P = 0.5000).

Conclusions:

Isolated orbit wall fractures are common in maxillofacial trauma and often require surgical repair. Concomitant ocular injury is common (31.8%) with this highest incidence occurring with lateral wall fractures (50%); however, statistical analysis did not demonstrate a significant relationship between the anatomic location of an isolated single-wall fracture and eye injuries.
MySurgeryRisk: Development and Validation of a Machine-learning Risk Algorithm for Major Complications and Death After Surgery
Authors: Bihorac Azra , Ozrazgat-Baslanti Tezcan , Ebadi Ashkan , Motaei Amir , Madkour Mohcine , Pardalos Panagote M. , Lipori Gloria , Hogan William R. , Efron Philip A. , Moore Frederick , Moldawer Lyle L. , Wang Daisy Zhe , Hobson Charles E. , Rashidi Parisa , Li Xiaolin , Momcilovic Petar
Published: February 2018

Objective:

To accurately calculate the risk for postoperative complications and death after surgery in the preoperative period using machine-learning modeling of clinical data.

Background:

Postoperative complications cause a 2-fold increase in the 30-day mortality and cost, and are associated with long-term consequences. The ability to precisely forecast the risk for major complications before surgery is limited.

Methods:

In a single-center cohort of 51,457 surgical patients undergoing major inpatient surgery, we have developed and validated an automated analytics framework for a preoperative risk algorithm (MySurgeryRisk) that uses existing clinical data in electronic health records to forecast patient-level probabilistic risk scores for 8 major postoperative complications (acute kidney injury, sepsis, venous thromboembolism, intensive care unit admission >48 hours, mechanical ventilation >48 hours, wound, neurologic, and cardiovascular complications) and death up to 24 months after surgery. We used the area under the receiver characteristic curve (AUC) and predictiveness curves to evaluate model performance.

Results:

MySurgeryRisk calculates probabilistic risk scores for 8 postoperative complications with AUC values ranging between 0.82 and 0.94 [99% confidence intervals (CIs) 0.81–0.94]. The model predicts the risk for death at 1, 3, 6, 12, and 24 months with AUC values ranging between 0.77 and 0.83 (99% CI 0.76–0.85).

Conclusions:

We constructed an automated predictive analytics framework for machine-learning algorithm with high discriminatory ability for assessing the risk of surgical complications and death using readily available preoperative electronic health records data. The feasibility of this novel algorithm implemented in real time clinical workflow requires further testing.
ABO-incompatible Living Donor Liver Transplantation With Rituximab and Total Plasma Exchange Does Not Increase Hepatocellular Carcinoma Recurrence
Authors: Kim Jong Man , Kwon Choon Hyuck David , Joh Jae-Won , Han Sangbin , Yoo Jeejin , Kim Kyunga , Sinn Dong Hyun , Choi Gyu-Seong , Gerber David A. , Egawa Hiroto , Lee Suk-Koo
Published: February 2018

Background

ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. This study compares hepatocellular carcinoma (HCC) recurrence in ABO-I LDLT with that in ABO-compatible (ABO-C) LDLT and explores the effects of rituximab prophylaxis and total plasma exchange on HCC recurrence after LDLT.

Methods

Two hundred forty patients with a diagnosis of HCC underwent LDLT between 2010 and 2015. Fifty-nine patients underwent ABO-I LDLT.

Results

Baseline, perioperative, and tumor characteristics did not vary between the 2 groups. The 1-, 2-, and 3-year disease-free survival rates in the ABO-I LDLT and ABO-C LDLT groups were 90.3%, 79.7%, and 73.3% and 86.7%, 79.0%, and 75.3%, respectively (P = 0.96). The overall patient survival rates for the same period in the ABO-I LDLT and ABO-C LDLT groups were 90.6%, 85.0%, and 81.9% and 88.0%, 83.5%, and 82.5%, respectively (P = 0.77). Hepatocellular carcinoma recurrence after LDLT was associated with preoperative α-fetoprotein greater than 35 ng/mL, increased tumor size, encapsulation, and microvascular invasion. ABO incompatibility was not related to HCC recurrence after LDLT.

Conclusions

Hepatocellular carcinoma recurrence and patient survival in the ABO-I LDLT group are comparable to those in the ABO-C LDLT group. Rituximab prophylaxis and total plasma exchange do not increase HCC recurrence after LT.
Developmental experience with anthropogenic noise hinders adult mate location in an acoustically signalling invertebrate
Authors: Gurule-Small Gabrielle A. , Tinghitella Robin M.
Published: February 2018

Phenotypic plasticity facilitates survival and reproduction in rapidly changing and novel environments. Traffic noise spectrally overlaps with (i.e. masks) the sounds used by many acoustically signalling organisms to locate and secure mates. To determine if pre-reproductive exposure to noise improves adult performance in noisy environments, we reared field crickets (
Teleogryllus oceanicus
) in one of three noise environments: masking traffic noise, traffic noise from which frequencies that spectrally overlap with the crickets' song were removed (non-masking), or silence. At reproductive maturity, we tested female mate location ability under one of the same three acoustic conditions. We found that exposure to noise during rearing hindered female location of mates, regardless of the acoustic environment at testing. Females reared in masking noise took 80% longer than females reared in silence to locate a simulated singing male who was less than 1 m away. Impaired mate location ability can be added to a growing list of fitness costs associated with anthropogenic noise, alongside reductions in pairing success, nesting success and offspring survival.
Body odour disgust sensitivity predicts authoritarian attitudes
Authors: Liuzza Marco Tullio , Lindholm Torun , Hawley Caitlin B. , Gustafsson Sendén Marie , Ekström Ingrid , Olsson Mats J. , Olofsson Jonas K.
Published: February 2018

Authoritarianism has resurfaced as a research topic in political psychology, as it appears relevant to explain current political trends. Authoritarian attitudes have been consistently linked to feelings of disgust, an emotion that is thought to have evolved to protect the organism from contamination. We hypothesized that body odour disgust sensitivity (BODS) might be associated with authoritarianism, as chemo-signalling is a primitive system for regulating interpersonal contact and disease avoidance, which are key features also in authoritarianism. We used well-validated scales for measuring BODS, authoritarianism and related constructs. Across two studies, we found that BODS is positively related to authoritarianism. In a third study, we showed a positive association between BODS scores and support for Donald Trump, who, at the time of data collection, was a presidential candidate with an agenda described as resonating with authoritarian attitudes. Authoritarianism fully explained the positive association between BODS and support for Donald Trump. Our findings highlight body odour disgust as a new and promising domain in political psychology research. Authoritarianism and BODS might be part of the same disease avoidance framework, and our results contribute to the growing evidence that contemporary social attitudes might be rooted in basic sensory functions.
An optimized approach for local de novo assembly of overlapping paired-end RAD reads from multiple individuals
Authors: Li Yu-Long , Xue Dong-Xiu , Zhang Bai-Dong , Liu Jin-Xian
Published: February 2018

Restriction site-associated DNA (RAD) sequencing is revolutionizing studies in ecological, evolutionary and conservation genomics. However, the assembly of paired-end RAD reads with random-sheared ends is still challenging, especially for non-model species with high genetic variance. Here, we present an efficient optimized approach with a pipeline software, RADassembler, which makes full use of paired-end RAD reads with random-sheared ends from multiple individuals to assemble RAD contigs. RADassembler integrates the algorithms for choosing the optimal number of mismatches within and across individuals at the clustering stage, and then uses a two-step assembly approach at the assembly stage. RADassembler also uses data reduction and parallelization strategies to promote efficiency. Compared to other tools, both the assembly results based on simulation and real RAD datasets demonstrated that RADassembler could always assemble the appropriate number of contigs with high qualities, and more read pairs were properly mapped to the assembled contigs. This approach provides an optimal tool for dealing with the complexity in the assembly of paired-end RAD reads with random-sheared ends for non-model species in ecological, evolutionary and conservation studies. RADassembler is available at https://github.com/lyl8086/RADscripts.
Forming three-dimensional closed shapes from two-dimensional soft ribbons by controlled buckling
Authors: Aoki Michio , Juang Jia-Yang
Published: February 2018

Conventional manufacturing techniques—moulding, machining and casting—exist to produce three-dimensional (3D) shapes. However, these industrial processes are typically geared for mass production and are not directly applicable to residential settings, where inexpensive and versatile tools are desirable. Moreover, those techniques are, in general, not adequate to process soft elastic materials. Here, we introduce a new concept of forming 3D closed hollow shapes from two-dimensional (2D) elastic ribbons by controlled buckling. We numerically and experimentally characterize how the profile and thickness of the ribbon determine its buckled shape. We find a 2D master profile with which various elliptical 3D shapes can be formed. More complex natural and artificial hollow shapes, such as strawberry, hourglass and wheel, can also be achieved via strategic design and pattern engraving on the ribbons. The nonlinear response of the post-buckling regime is rationalized through finite-element analysis, which shows good quantitative agreement with experiments. This robust fabrication should complement conventional techniques and provide a rich arena for future studies on the mechanics and new applications of elastic hollow structures.
Texture evolution and mechanical behaviour of irradiated face-centred cubic metals
Authors: Chen L. R. , Xiao X. Z. , Yu L. , Chu H. J. , Duan H. L.
Published: February 2018

A physically based theoretical model is proposed to investigate the mechanical behaviour and crystallographic texture evolution of irradiated face-centred cubic metals. This model is capable of capturing the main features of irradiated polycrystalline materials including irradiation hardening, post-yield softening and plasticity localization. Numerical results show a good agreement with experimental data for both unirradiated and irradiated stress–strain relationships. The study of crystallographic texture reveals that the initial randomly distributed texture of unirradiated metals under tensile loading can evolve into a mixture of [111] and [100] textures. Regarding the irradiated case, crystallographic texture develops in a different way, and an extra part of [110] texture evolves into [100] and [111] textures. Thus, [100] and [111] textures become dominant more quickly compared with those of the unirradiated case for the reason that [100] and [111]-oriented crystals have higher strength, and their plastic deformation behaviours are more active than other oriented crystals. It can be concluded that irradiation-induced defects can affect both the mechanical behaviour and texture evolution of metals, both of which are closely related to irradiation hardening.
Expression profiling across wild and cultivated tomatoes supports the relevance of early miR482/2118 suppression for
Phytophthora
resistance
Authors: de Vries Sophie , Kukuk Andreas , von Dahlen Janina K. , Schnake Anika , Kloesges Thorsten , Rose Laura E.
Published: February 2018

Plants possess a battery of specific pathogen resistance (
R-
)genes. Precise
R-
gene regulation is important in the presence and absence of a pathogen. Recently, a microRNA family, miR482/2118, was shown to regulate the expression of a major class of
R-
genes
,
nucleotide-binding site leucine-rich repeats (
NBS-LRRs
). Furthermore, RNA silencing suppressor proteins, secreted by pathogens, prevent the accumulation of miR482/2118, leading to an upregulation of
R-
genes. Despite this transcriptional release of
R
-genes, RNA silencing suppressors positively contribute to the virulence of some pathogens
.
To investigate this paradox, we analysed how the regulation of
NBS-LRRs
by miR482/2118 has been shaped by the coevolution between
Phytophthora infestans
and cultivated and wild tomatoes. We used degradome analyses and qRT-PCR to evaluate and quantify the co-expression of miR482/2118 and their
NBS-LRR
targets. Our data show that miR482/2118-mediated targeting contributes to the regulation of
NBS-LRRs
in
Solanum lycopersicum.
Based on miR482/2118 expression profiling in two additional tomato species—with different coevolutionary histories with
P. infestans
—we hypothesize that pathogen-mediated RNA silencing suppression is most effective in the interaction between
S. lycopersicum
and
P. infestans
. Furthermore, an upregulation of miR482/2118 early in the infection may increase susceptibility to
P. infestans
.
Restoration and repair of Earth's damaged ecosystems
Authors: Jones Holly P. , Jones Peter C. , Barbier Edward B. , Blackburn Ryan C. , Rey Benayas Jose M. , Holl Karen D. , McCrackin Michelle , Meli Paula , Montoya Daniel , Mateos David Moreno
Published: February 2018

Given that few ecosystems on the Earth have been unaffected by humans, restoring them holds great promise for stemming the biodiversity crisis and ensuring ecosystem services are provided to humanity. Nonetheless, few studies have documented the recovery of ecosystems globally or the rates at which ecosystems recover. Even fewer have addressed the added benefit of actively restoring ecosystems versus allowing them to recover without human intervention following the cessation of a disturbance. Our meta-analysis of 400 studies worldwide that document recovery from large-scale disturbances, such as oil spills, agriculture and logging, suggests that though ecosystems are progressing towards recovery following disturbances, they rarely recover completely. This result reinforces conservation of intact ecosystems as a key strategy for protecting biodiversity. Recovery rates slowed down with time since the disturbance ended, suggesting that the final stages of recovery are the most challenging to achieve. Active restoration did not result in faster or more complete recovery than simply ending the disturbances ecosystems face. Our results on the added benefit of restoration must be interpreted cautiously, because few studies directly compared different restoration actions in the same location after the same disturbance. The lack of consistent value added of active restoration following disturbance suggests that passive recovery should be considered as a first option; if recovery is slow, then active restoration actions should be better tailored to overcome specific obstacles to recovery and achieve restoration goals. We call for a more strategic investment of limited restoration resources into innovative collaborative efforts between scientists, local communities and practitioners to develop restoration techniques that are ecologically, economically and socially viable.
Vocal contagion of emotions in non-human animals
Authors: Briefer Elodie F.
Published: February 2018

Communicating emotions to conspecifics (emotion expression) allows the regulation of social interactions (e.g. approach and avoidance). Moreover, when emotions are transmitted from one individual to the next, leading to state matching (emotional contagion), information transfer and coordination between group members are facilitated. Despite the high potential for vocalizations to influence the affective state of surrounding individuals, vocal contagion of emotions has been largely unexplored in non-human animals. In this paper, I review the evidence for discrimination of vocal expression of emotions, which is a necessary step for emotional contagion to occur. I then describe possible proximate mechanisms underlying vocal contagion of emotions, propose criteria to assess this phenomenon and review the existing evidence. The literature so far shows that non-human animals are able to discriminate and be affected by conspecific and also potentially heterospecific (e.g. human) vocal expression of emotions. Since humans heavily rely on vocalizations to communicate (speech), I suggest that studying vocal contagion of emotions in non-human animals can lead to a better understanding of the evolution of emotional contagion and empathy.
Diversity-dependent evolutionary rates in early Palaeozoic zooplankton
Authors: Foote Michael , Cooper Roger A. , Crampton James S. , Sadler Peter M.
Published: February 2018

The extent to which biological diversity affects rates of diversification is central to understanding macroevolutionary dynamics, yet no consensus has emerged on the importance of diversity-dependence of evolutionary rates. Here, we analyse the species-level fossil record of early Palaeozoic graptoloids, documented with high temporal resolution, to test directly whether rates of diversification were influenced by levels of standing diversity within this major clade of marine zooplankton. To circumvent the statistical regression-to-the-mean artefact, whereby higher- and lower-than-average values of diversity tend to be followed by negative and positive diversification rates, we construct a non-parametric, empirically scaled, diversity-independent null model by randomizing the observed diversification rates with respect to time. Comparing observed correlations between diversity and diversification rate to those expected from this diversity-independent model, we find evidence for negative diversity-dependence, accounting for up to 12% of the variance in diversification rate, with maximal correlation at a temporal lag of approximately 1 Myr. Diversity-dependence persists throughout the Ordovician and Silurian, despite a major increase in the strength and frequency of extinction and speciation pulses in the Silurian. By contrast to some previous work, we find that diversity-dependence affects rates of speciation and extinction nearly equally on average, although subtle differences emerge when we compare the Ordovician and Silurian.
Dynamic interplay of innate and adaptive immunity during sterile retinal inflammation: Insights from the transcriptome
Authors: Natoli Riccardo , Mason Elizabeth , Jiao Haihan , Chuah Aaron , Patel Hardip , Fernando Nilisha , Valter Krisztina , Wells Christine A. , Provis Jan , Rutar Matt
Published: February 2018

The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu amongst the broad leukocyte infiltrate, and the gene networks which construct these responses, are poorly described in the eye. Using photo-oxidative damage in a rodent model of subretinal inflammation, we employed a novel RNA-sequencing framework to map the global gene network signature of retinal leukocytes. This revealed a previously uncharted interplay of adaptive immunity during subretinal inflammation, including prolonged enrichment of myeloid and lymphocyte migration, antigen presentation, and the alternative arm of the complement cascade involving Factor B. We demonstrate Factor B-deficient mice are protected against macrophage infiltration and subretinal inflammation. Suppressing the drivers of retinal leukocyte proliferation, or their capacity to elicit complement responses, may help preserve retinal structure and function during sterile inflammation in diseases such as AMD.
ALotus japonicusE3 ligase interacts with the Nod factor receptor 5 and positively regulates nodulation
Authors: Tsikou Daniela , Ramirez Estrella E. , Psarrakou Ioanna S. , Wong Jaslyn E. , Jensen Dorthe B. , Isono Erika , Radutoiu Simona , Papadopoulou Kalliope K.
Published: February 2018

Post-translational modification of receptor proteins is involved in activation and de-activation of signaling systems in plants. Both ubiquitination and deubiquitination have been implicated in plant interactions with pathogens and symbionts. Here we presentLjPUB13, a PUB-ARMADILLO repeat E3 ligase that specifically ubiquitinates the kinase domain of the Nod Factor receptor NFR5 and has a direct role in nodule organogenesis events inLotus japonicus. Phenotypic analyses of three LORE1 retroelement insertion plant lines revealed thatpub13plants display delayed and reduced nodulation capacity and retarded growth.LjPUB13expression is spatially regulated during symbiosis withMesorhizobium loti, with increased levels in young developing nodules. Thus,LjPUB13 is an E3 ligase with a positive regulatory role during the initial stages of nodulation inL. japonicus.
Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling
Authors: McClatchy Daniel B. , Ma Yuanhui , Liem David A. , Ng Dominic C.M. , Ping Peipei , Yates John R.
Published: February 2018

Maladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has the potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.
ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls
Authors: Hendricks AE , Billups S , Pike HNC , Farooqi IS , Zeggini E , Santorico SA , Barroso I , Dupuis J
Published: February 2018

A primary goal of the recent investment in sequencing is to detect novel genetic associations in health and disease improving the development of treatments and playing a critical role in precision medicine. While this investment has resulted in an enormous number of sequenced genomes, individual studies of complex traits are often smaller and underpowered to detect rare variant genetic associations. Existing genetic resources such as the Exome Aggregation Consortium (>60,000 exomes) and the Genome Aggregation Database (~140,000 sequenced samples) could be used as controls in these studies. Fully utilizing these and other existing sequencing resources has the potential to increase power and could be especially useful in studies where resources to sequence additional samples are limited. However, to date, these large, publicly available genetic resources remain underutilized, or even misused, in large part due to the lack of statistical methods that can appropriately use this summary level data. We present a new method to incorporate external controls in case-control analysis called ProxECAT (Proxy External Controls Association Test). ProxECAT estimates enrichment of rare variants within a gene region using internally sequenced cases and external controls. We evaluated ProxECAT in simulations and empirical analyses of obesity cases using both low-depth of coverage (7x) whole-genome sequenced controls and ExAC as controls. We find that ProxECAT maintains the expected type I error rate with increased power as the number of external controls increases. With an accompanying R package, ProxECAT enables the use of publicly available allele frequencies as external controls in case-control analysis.
Emergence of evolutionary stable communities through eco-evolutionary tunneling
Authors: Kotil Seyfullah Enes , Vetsigian Kalin
Published: February 2018

Ecological and evolutionary dynamics of communities are inexorably intertwined. The ecological state determines the fate of newly arising mutants, and mutations that increase in frequency can reshape the ecological dynamics. Evolutionary game theory and its extensions within adaptive dynamics (AD) have been the mathematical frameworks for understanding this interplay, leading to notions such as Evolutionary Stable States (ESS) in which no mutations are favored, and evolutionary branching points near which the population diversifies. A central assumption behind these theoretical treatments has been that mutations are rare so that the ecological dynamics has time to equilibrate after every mutation. A fundamental question is whether qualitatively new phenomena can arise when mutations are frequent. Here we describe an adaptive diversification process that robustly leads to complex ESS, despite the fact that such communities are unreachable through a step-by-step evolutionary process. Rather, the system as a whole tunnels between collective states over a short time scale. The tunneling rate is a sharply increasing function of the rate with which mutations arise in the population. This makes the emergence of ESS communities virtually impossible in small populations, but generic in large ones. Moreover, communities emerging through this process can spatially spread as single replication units that outcompete other communities. Overall, this work provides a qualitatively new mechanism for adaptive diversification and shows that complex structures can generically evolve even when no step-by-step evolutionary path exists.
Lung Cancer Explorer (LCE): an open web portal to explore gene expression and clinical associations in lung cancer
Authors: Cai Ling , Lin ShinYi , Zhou Yunyun , Yang Lin , Ci Bo , Zhou Qinbo , Luo Danni , Yao Bo , Tang Hao , Allen Jeffrey , Huffman Kenneth , Gazdar Adi , Heymach John , Wistuba Ignacio , Xiao Guanghua , Minna John , Xie Yang
Published: February 2018

We constructed a lung cancer-specific database housing expression data and clinical data from over 6,700 patients in 56 studies. Expression data from 23 “whole-genome” based platforms were carefully processed and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer database, we created an open access web resource – the Lung Cancer Explorer (LCE), which enables researchers and clinicians to explore these data and perform analyses. Users can perform meta-analyses on LCE to gain a quick overview of the results on tumor vs normal differential gene expression and expression-survival association. Individual dataset-based survival analysis, comparative analysis, and correlation analysis are also provided with flexible options to allow for customized analyses from the user.
Predicting Evolutionarily Stable Strategies from Functional Responses of Sonoran Desert Annuals to Precipitation
Authors: Cuello William S. , Gremer Jennifer R. , Trimmer Pete C. , Sih Andrew , Schreiber Sebastian J.
Published: February 2018

For many decades, researchers have studied how plants use bet-hedging strategies to insure against unpredictable, unfavorable conditions. We improve upon earlier analyses by explicitly accounting for how variable precipitation affects annual plant species’ bet-hedging strategies. We consider how the survival rates of dormant seeds (in a ‘seed bank’) interact with precipitation responses to influence optimal germination strategies. Specifically, we incorporate how response to resource availability (i.e. the amount of offspring (seeds) generated per plant in response to variation in desert rainfall) influences the evolution of germination fractions. Using data from 10 Sonoran Desert annual plants, we develop models that explicitly include these responses to model fitness as a function of precipitation. For each of the species, we identify the predicted evolutionarily stable strategies (ESS) for the fraction of seeds germinating each year and then compare our estimated ESS values to the observed germination fractions. We also explore the relative importance of seed survival and precipitation responses in shaping germination strategies by regressing ESS values and observed germination fractions against these traits. We find that germination fractions are lower for species with higher seed survival, with lower reproductive success in dry years, and with better yield responses in wet years. These results illuminate the evolution of bethedging strategies in an iconic system, and provide a framework for predicting how current and future environmental conditions may reshape those strategies.
Fierce selection and interference in B-cell repertoire response to chronic HIV-1
Authors: Nourmohammad Armita , Otwinowski Jakub , Łuksza Marta , Mora Thierry , Walczak Aleksandra M
Published: February 2018

During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host’s adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen engaging CDRs of B-cell receptors (BCRs) are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix.
Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium
Authors: Zhou Ling , Niu Xuping , Liang Jiannan , Li Junqin , Li Jiao , Cheng Yueai , Meng Yanfeng , Wang Qiang , Yang Xiaoli , Wang Gang , Shi Yu , Dang Erle , Zhang Kaiming
Published: February 2018

Objective

To directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases.

Methods

After separation by adherent culture, VEC line supernatant, vascular endothelial growth factor (VEGF), bone morphogenetic protein-4 and hypoxia were used for the differentiation of VECs from DMSCs. The cell type was authenticated by flow cytometry, matrigel angiogenesis assay in vitro, and immunofluorescent staining during differentiation. The VEGF concentration was investigated by enzyme-linked immunosorbent assay.

Results

After 28 days of differentiation, the cell surface marker CD31 was significantly positive (80%-90%) by flow cytometry in the VEC line-conditioned culture, which was significantly higher than in the other groups. Differentiated DMSCs had the ability to ingest Dil-ac-LDL and vascularize in the conditioned culture, but not in the other groups. In the VEC line supernatant, the concentration of VEGF was very low. The VEGF concentration changed along with the differentiation into VECs in the medium of the conditioned culture group.

Conclusion

VEC line supernatant can induce the differentiation of DMSCs into VECs, possibly through the pathway except VEGF.
Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus
Authors: Taracena Mabel L. , Bottino-Rojas Vanessa , Talyuli Octavio A.C. , Walter-Nuno Ana Beatriz , Oliveira José Henrique M. , Angleró-Rodriguez Yesseinia I. , Wells Michael B. , Dimopoulos George , Oliveira Pedro L. , Paiva-Silva Gabriela O.
Published: February 2018

Aedes aegypti is the vector of some of the most important vector-borne diseases like Dengue, Chikungunya, Zika and Yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in ROS production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.
Mitochondrial ATP synthase dimers spontaneously self-associate driven by a long-ranged membrane-induced force
Authors: Anselmi Claudio , Davies Karen M. , Faraldo-Gómez José D.
Published: February 2018

ATP synthases populate the inner membranes of mitochondria, where they produce the majority of the ATP required by the cell. Cryo-electron tomograms of these membranes from yeast to vertebrates have consistently revealed a very precise organization of these enzymes. Rather than being scattered throughout the membrane, the ATP synthases form dimers, and these dimers are organized into rows that extend for hundreds of nanometers. These rows are only observed in the membrane invaginations known as cristae, specifically along their sharply curved edges. Although the presence of these macromolecular structures has been irrefutably linked to the proper development of cristae morphology, it has been unclear what drives the formation of the rows and why they are specifically localized in the cristae. We present the result of a quantitative molecular-simulation analysis that strongly suggests that the ATP synthase dimers organize into rows spontaneously, driven by a long-ranged attractive force that results from relief in the overall elastic strain of the membrane. This strain is caused by the V-like shape of the dimers, unique among membrane-protein complexes, which induces a strong deformation in the surrounding membrane. The process of row formation is therefore not a result of protein-protein interactions, or of a specific lipid composition of the membrane. We further hypothesize that once assembled, the ATP synthase dimer rows prime the inner mitochondrial membrane to develop folds and invaginations, by causing macroscopic membrane ridges that ultimately become the cristae edges. In this view, mitochondrial ATP synthases would contribute to the generation of a morphology that maximizes the surface area of the inner membrane, and thus ATP production. Finally, we outline the key experiments that would be required to verify or refute this hypothesis.
VideoTagger: User-Friendly Software for Annotating Video Experiments of Any Duration
Authors: Rennert Peter , Aodha Oisin Mac , Piper Matthew , Brostow Gabriel
Published: February 2018

Background

Scientific insight is often sought by recording and analyzing large quantities of video. While easy access to cameras has increased the quantity of collected videos, the rate at which they can be analyzed remains a major limitation. Often, bench scientists struggle with the most basic problem that there is currently no user-friendly, flexible, and open source software tool with which to watch and annotate these videos.

Results

We have created the VideoTagger tool to address these and many of the other associated challenges of video analysis. VideoTagger allows non-programming users to efficiently explore, annotate, and visualize large quantities of video data, within their existing experimental protocols. Further, it is built to accept programmed plugins written in Python, to enable seamless integration with other sophisticated computer-aided analyses.

We tested VideoTagger ourselves, and have a growing base of users in other scientific disciplines. Capitalising on the unique features of VideoTagger to play back infinite lengths of video footage at various speeds, we annotated 39h of a Drosophila melanogaster lifespan video, at approximately 10-15x faster than real-time. We then used these labels to train a machine-learning plugin, which we used to annotate an additional 538h of footage automatically. In this way, we found that flies fall over spontaneously with increasing frequency as they age, and also spend longer durations struggling to right themselves. Ageing in flies is typically defined by length of life. We propose that this new mobility measure of ageing could help the discovery of mechanisms in biogerontology, refining our definition of what healthy ageing means in this extremely small, but widely used, invertebrate.

Conclusions

We show how VideoTagger is sufficiently flexible for studying lengthy and/or numerous video experiments, thus directly improving scientists’ productivity across varied domains.
The tumor suppressor FBW7 and the vitamin D receptor are mutual cofactors
Authors: Salehi-Tabar Reyhaneh , Memari Babak , Wong Hilary , Rochel Natacha , White John H.
Published: February 2018

The E3 ligase FBW7 targets drivers of cell cycle progression such as c-MYC for proteasomal degradation. It is frequently mutated in cancer, and is a tumor suppressor. Extensive epidemiological data links vitamin D deficiency to increased incidence of several cancers, although the underlying cancer-preventive mechanisms are poorly understood. Here, we show that hormonal 1,25-dihydroxyvitamin D3 (1,25D) rapidly stimulates the interaction of the VDR with FBW7, and that of FBW7 with c-MYC. In contrast, it blocks the association of FBW7 with c-MYC antagonist MXD1. 1,25D also enhances the association of FBW7, proteasome subunits, and ubiquitin with DNA-bound c-MYC, consistent with induced degradation of c-MYC on DNA. In addition to c-MYC, 1,25D accelerates the turnover of other FBW7 target proteins. Intriguingly, FBW7 is essential for optimalVDRgene expression. It is also recruited to VDR targets genes, and its depletion attenuates 1,25D-stimulated VDR DNA binding, transactivation, and cell cycle arrest. Thus, the VDR and FBW7 are mutual cofactors, which provides a molecular basis for the cancer-preventive actions of vitamin D through accelerated turnover of FBW7 target proteins.
HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer
Authors: Chen Yi-Ting , Wang Tso-Wen , Chang Tsung-Hao , Hsu Teng-Po , Chi Jhih-Ying , Hsiao Yu-Wei , Li Chien-Feng , Wang Ju-Ming
Published: February 2018

Pancreatic cancer is refractory and characterized by extensively surrounding- and intra-tumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Activation of PSCs plays a pivotal role for developing fibrotic reactions to affect themselves or pancreatic cancer cells (PCCs). In the current study, we demonstrated that hepatoma-derived growth factor (HDGF) was secreted from transforming growth factor-β1 (TGF-β1)-treated PSCs. We found that HDGF contributed to anti-apoptosis of PSCs and led to synthesis and depositions of extracellular matrix proteins for stabilizing PSCs/PCCs tumor foci. CCAAT/enhancer binding protein δ (CEBPD) responds to TGF-β1 through a reciprocal loop regulation and further activated hypoxia inducible factor-1α (HIF-1α) contributed to up-regulation ofHDGFgene. It agrees with the observation that severe stromal growth positively correlated with stromal HDGF and CEBPD in pancreatic cancer specimens. Collectively, the identification of TGF-β1-activated CEBPD/HIF-1α/HDGF axis provides new insights for the novel discoveries of HDGF in anti-apoptosis and pro-fibrosis of PSCs and outgrowth of pancreatic cancer cells.
MACPET: Model-based Analysis for ChIA-PET
Authors: Vardaxis Ioannis , Drabløs Finn , Rye Morten B. , Lindqvist Bo Henry
Published: February 2018

We present Model-based Analysis for ChIA-PET (MACPET) which analyzes paired-end read sequences provided by ChIA-PET for finding binding sites of a protein of interest. MACPET uses information from both tags of each PET and searches for binding sites in a two-dimensional space, while taking into account different noise levels in different genomic regions. MACPET shows favorable results compared to MACS in terms of motif occurrence, spatial resolution and false discovery rate. Significant binding sites discovered by MACPET are involved in a higher number of significant 3D interactions than those discovered by MACS. MACPET is freely available on Bioconductor.