bluuebunny/crossref_metadata_2025 huggingface dataset:
Tourniquet use is not associated with limb loss following military lower extremity arterial trauma
Authors: Kauvar David S. , Miller Diane , Walters Thomas J.
Published: July 2018

BACKGROUND

The effect of battlefield extremity tourniquet (TK) use on limb salvage and long-term complications following vascular repair is unknown. This study explores the influence of TK use on limb outcomes in military lower extremity arterial injury.

METHODS

The study database includes cases of lower extremity vascular injury from 2004 to 2012 with data recorded until discharge from military service. We analyzed all limbs with at least one named arterial injury from the femoral to the tibial level. Tourniquet (TK) and no TK (NTK) groups were identified. Univariate analyses were performed with significance set at p ≤ 0.05.

RESULTS

A total of 455 cases were included, with 254 (56%) having a TK for a median of 60 minutes (8–270 minutes). Explosive injuries (53%) and gunshot wounds (26%) predominated. No difference between TK and NTK was present in presence of fracture, level of arterial injury, type of arterial repair, or concomitant venous injury. More nerve injuries were present in the TK group, and Abbreviated Injury Scale extremity and Mangled Extremity Severity Score tended toward greater injury severity. Amputation and mortality rates did not differ between groups, but the incidence of severe edema, wound infection, and foot drop was higher in the TK group. Vascular above-knee amputation, arterial repair complication, and severe edema were higher in the TK group also (p = 0.10). Tourniquet duration of 60 minutes or longer was not associated with increased amputations, but more rhabdomyolysis was present.

CONCLUSION

Field TK use is associated with wound infection and neurologic compromise but not limb loss. This may be due to a more severe injury profile among TK limbs. Increased TK times may predispose to systemic, but not limb, complications.

LEVEL OF EVIDENCE

Therapeutic/care management, level IV.
Improved Gray Matter Atrophy Detection in Alzheimer Disease in Chinese Populations Using Chinese Brain Template
Authors: Jia Xiuqin , Shi Lin , Qian Tianyi , Li Ying , Wang Defeng , Liang Peipeng , Li Kuncheng
Published: July 2018

Objective:

This study aimed to test the hypothesis that the statistical Chinese brain template would be more effective to detect gray matter (GM) changes in patients with Alzheimer disease (AD) in Chinese populations.

Materials and Methods:

In total, 50 patients with AD and 50 sex-matched and age-matched healthy controls were included in this study. Chinese2020, a typical statistical Chinese brain template, and MNI152, a typical Caucasian template were used for spatial normalization respectively. The GM volume alterations in patients with AD were examined by using voxel-based morphometry with education level and total intracranial volume as nuisance variables. The GM proportions of the identified brain areas with group difference were compared.

Results:

By using Chinese2020 and MNI152, significant GM atrophies in patients with AD were commonly detected in the bilateral medial temporal lobe, lateral temporal lobe, inferior/medial frontal cortex, as well as left thalamus. However, higher GM percentages of detected regions were acquired when Chinese2020 was used rather than MNI152. Furthermore, stronger statistical powers in the detected clusters were observed using Chinese2020 than MNI152. In addition, the laterality index analysis showed the bilateral atrophies with no hemispheric laterality in the para/hippocampus when using population-specific brain atlas (ie, Chinese2020).

Conclusions:

These findings indicated that applying the population-specific brain atlas to neuroimaging studies may achieve higher accuracy in activation detection. This may have implications to the imaging study of neurodegenerative diseases.
Online Theta Frequency Transcranial Alternating Current Stimulation for Cognitive Remediation in Schizophrenia
Authors: Sreeraj Vanteemar S. , Shivakumar Venkataram , Sowmya Selvaraj , Bose Anushree , Nawani Hema , Narayanaswamy Janardhanan C. , Venkatasubramanian Ganesan
Published: July 2018

Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that uses low-intensity alternating current, has been postulated to be a potential therapeutic option in treating the cognitive deficits in schizophrenia. Transcranial alternating current stimulation synchronizes the neural oscillations to the applied stimulation frequency in the stimulated cortical regions. In this report, we have reviewed the literature pertinent to the clinical application of tACS in psychiatric disorders; in addition, we have described the clinical use of online theta tACS in a schizophrenia patient with cognitive deficits. Online theta tACS led to improvement in working memory, attention, processing speed, and emotional processing. The beneficial effect of tACS persisted during reassessment of the patient after 50 days. Transcranial alternating current stimulation, given its noninvasiveness, safety, and ease of administration, has the potential to ameliorate cognitive deficits in neuropsychiatric disorders like schizophrenia.
A different state of mind: neural activity related to volitionally up- versus downregulating cortical excitability
Authors: Ruddy Kathy , Balsters Joshua , Mantini Dante , Liu Quanying , Kassraian-Fard Pegah , Enz Nadja , Mihelj Ernest , Chander Bankim , Soekadar Surjo R. , Wenderoth Nicole
Published: July 2018

To date there exists no reliable method to non-invasively upregulate or downregulate the state of the resting motor system over a large dynamic range. Here we show that an operant conditioning paradigm which provides neurofeedback of the size of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS), enables participants to self-modulate their own brain state. Following training, participants were able to robustly increase (by 83.8%) and decrease (by 30.6%) their MEP amplitudes. This volitional up-versus down-regulation of corticomotor excitability caused an increase of late-cortical disinhibition (LCD), a TMS derived read-out of presynaptic GABAB disinhibition, which was accompanied by an increase of gamma and a decrease of alpha oscillations in the trained hemisphere. This approach paves the way for future investigations into how altered brain state influences motor neurophysiology and recovery of function in a neurorehabilitation context.
Applying Inter-rater Reliability to Improve Consistency in Classifying PhD Career Outcomes
Authors: Stayart C. Abigail , Brandt Patrick D. , Brown Abigail M. , Hutto Tamara , Layton Rebekah L. , Petrie Kimberly A. , Flores-Kim Emma N. , Peña Christopher G. , Fuhrmann Cynthia N. , Monsalve Gabriela C.
Published: July 2018

In the past year, there has been an exciting groundswell of national efforts to integrate multiple taxonomies for the transparent dissemination and analysis of PhD career outcomes. In this study, we leveraged the unique resources of the Broadening Experiences in Scientific Training Consortium to examine the reliability of the three-tiered Unified Career Outcomes Taxonomy (UCOT v.2017) that was collaboratively developed at a meeting convened by Rescuing Biomedical Research in August 2017. Using an amended version of the UCOT v.2017 (UCOT v.2017-rev1) and a new Supplementary Guidance document, we categorized over 570 PhD alumni records from three different universities. Utilizing Krippendorff’s alpha to measure the interrater reliability from nine different individuals, we determined moderate to robust reproducibility within the first two tiers of the taxonomy (Workforce Sector and Career Type); however, the reliability for the third tier (Job Function) did not meet established standards. The team identified significant sources of error, revised category definitions, improved coder training materials and processes, and tested for improved reliability through coding 219 PhD alumni records using the revised taxonomy, UCOT v.2017-rev2. Our results revealed that the changes introduced in UCOT v.2017-rev2 improved inter-rater reliability in all three tiers, and either met or exceeded the acceptable standards for reliability. A final set of clarifications were made to UCOT v.2017-rev2, resulting in UCOT v.2018 and a Finalized Guidance document. Our findings underscore the importance of carefully developing guidance documents to aid coders in the reliable and consistent categorization of alumni career outcomes. We propose periodic assessment of the UCOT v.2018 to address the natural evolution of PhD careers in the global workforce. Ultimately, we hope that UCOT v.2018 will aid in the classification and dissemination of alumni career outcomes that is essential to educating trainees, institutions, and agencies about the diversity of career options for PhDs, and therein empower all PhDs to pursue the careers of their choice.
Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.
Authors: Madgwick Alicia , Magri Marta Silvia , Dantec Christelle , Gailly Damien , Fiuza Ulla-Maj , Guignard Leo , Hettinger Sabrina , Gomez-Skarmeta Jose Luis , Lemaire Patrick
Published: July 2018

Ascidian species of the Phallusia and Ciona genera are distantly related, their last common ancestor dating several hundred million years ago. Although their genome sequences have extensively diverged since this radiation, Phallusia and Ciona species share almost identical early morphogenesis and stereotyped cell lineages. Here, we explored the evolution of transcriptional control between P. mammillata and C. robusta. We combined genome-wide mapping of open chromatin regions in both species with a comparative analysis of the regulatory sequences of a test set of 10 pairs of orthologous early regulatory genes with conserved expression patterns. We find that ascidian chromatin accessibility landscapes obey similar rules as in other metazoa. Open-chromatin regions are short, highly conserved within each genus and cluster around regulatory genes. The dynamics of chromatin accessibility and closest-gene expression are strongly correlated during early embryogenesis. Open-chromatin regions are highly enriched in cis-regulatory elements: 73% of 49 open chromatin regions around our test genes behaved as either distal enhancers or proximal enhancer/promoters following electroporation in Phallusia eggs. Analysis of this datasets suggests a pervasive use in ascidians of shadow enhancers with partially overlapping activities. Cross-species electroporations point to a deep conservation of both the trans-regulatory logic between these distantly-related ascidians and the cis-regulatory activities of individual enhancers. Finally, we found that the relative order and approximate distance to the transcription start site of open chromatin regions can be conserved between Ciona and Phallusia species despite extensive sequence divergence, a property that can be used to identify orthologous enhancers, whose regulatory activity can partially diverge.
Integration and modularity in Procrustes shape data: is there a risk of spurious results?
Authors: Cardini Andrea
Published: July 2018

Studies of morphological integration and modularity are a hot topic in evolutionary developmental biology. Geometric morphometrics using Procrustes methods offers powerful tools to quantitatively investigate morphological variation and, within this methodological framework, a number of different methods has been put forward to test if different regions within an anatomical structure behave like modules or,vice versa, are highly integrated and covary strongly. Although some exploratory techniques do not requirea priorimodules, commonly modules are specified in advance based on prior knowledge. Once this is done, most of the methods can be applied either by subdividing modules and performing separate Procrustes alignments or by splitting shape coordinates of anatomical landmarks into modules after a common superimposition. This second approach is particularly interesting because, contrary to completely separate blocks analyses, it preserves information on relative size and position of the putative modules. However, it also violates one of the fundamental assumptions on which Procrustes methods are based, which is that one should not analyse or interpret subsets of landmarks from a common superimposition, because the choice of that superimposition is purely based on statistical convenience (although with sound theoretical foundations) and not on a biological model of variance and covariance. In this study, I offer a first investigation of the effects of testing integration and modularity within a configuration of commonly superimposed landmarks using some of the most widely employed statistical methods available to this aim. When applied to simulated shapes with random non-modular isotropic variation, standard methods frequently recovered significant but arbitrary patterns of integration and modularity. Re-superimposing landmarks within each module, before testing integration or modularity, generally removes this artifact. The study, although preliminary and exploratory in nature, raises an important issue and indicates an avenue for future research. It also suggests that great caution should be exercised in the application and interpretation of findings from analyses of modularity and integration using Procrustes shape data, and that issues might be even more serious using some of the most common methods for handling the increasing popular semilandmark data used to analyse 2D outlines and 3D surfaces.
Multivariate Stochastic Volatility Modeling of Neural Data
Authors: Phan Tung D. , Wacther Jessica A. , Solomon Ethan A. , Kahana Michael J.
Published: July 2018

Because multivariate autoregressive models have failed to adequately account for the complexity of neural signals, researchers have predominantly relied on non-parametric methods when studying the relations between brain and behavior. Using medial temporal lobe (MTL) recordings from 96 neurosurgical patients, we show that time series models with volatility described by a multivariate stochastic latent-variable process and lagged interactions between signals in different brain regions provide new insights into the dynamics of brain function. The implied volatility inferred from our process positively correlates with high-frequency spectral activity, a signal that correlates with neuronal activity. We show that volatility features derived from our model can reliably decode memory states, and that this classifier performs as well as those using spectral features. Using the directional connections between brain regions during complex cognitive process provided by the model, we uncovered perirhinal-hippocampal desynchronization in the MTL regions that is associated with successful memory encoding.
Towards personalized computer simulation of breast cancer treatment: a multi-scale pharmacokinetic and pharmacodynamic model informed by multi-type patient data
Authors: Lai Xiaoran , Geier Oliver M , Fleischer Thomas , Garred Øystein , Borgen Elin , Funke Simon Wolfgang , Kumar Surendra , Elisabeth Rognes Marie , Seierstad Therese , Børresen-Dale Anne-Lise , Kristensen Vessela N. , Engebraaten Olav , Köhn-Luque Alvaro , Frigessi Arnoldo
Published: July 2018

Mathematical modeling and simulation have emerged as a potentially powerful, time and cost effective approach to personalized cancer treatment. The usefulness of mechanistic models to disentangle complex multi-scale cancer processes such as treatment response has been widely acknowledged. However, a major barrier for multi-scale models to predict the outcomes of therapeutic regimens in a particular patient lies in their initialization and parameterization which need to reflect individual cancer characteristics accurately. In this study we use multi-type routinely acquired measurements on a single breast tumor, including histopathology, magnetic resonance imaging, and molecular profiling to personalize parts of a complex multi-scale model of breast cancer treated with chemotherapeutic and anti-angiogenic agents. We model the dynamics of drugs in tissue (pharmacokinetics) and the corresponding effects on their targets (pharmacodynamics). We developed a open-source computer program that simulates cross-sections of tumors under 12-week therapy regimes and use it to individually reproduce and elucidate treatment outcomes of four patients. For two of the tumors that did not respond to therapy, we used model simulations to suggest alternative regimes, depending on their individual characteristics, with improved outcomes. We found that more frequent doses of chemothereapy reduce tumor burden in a low proliferative tumor while lower doses of anti-angiogenic agents improve drug penetration in a poorly perfused tumor. In addition to bridge multi-type clinical data to shed light on individual treatment outcomes, our approach identified a few tumor-related aspects that need to be clinically portraited better to allow for future model-driven personalized cancer therapy.
State-specific individualized functional networks form a predictive signature of brain state
Authors: Salehi Mehraveh , Karbasi Amin , Barron Daniel S. , Scheinost Dustin , Todd Constable R.
Published: July 2018

There is extensive evidence that human brain functional organization is dynamic, varying within a subject as the brain switches between tasks demands. This functional organization also varies across subjects, even when they are all engaged in similar tasks. Currently, we lack a comprehensive model that unifies the two dimensions of variation (brain state and subject). Using fMRI data obtained across multiple task-evoked and rest conditions (which we operationally define as brain states) and across multiple subjects, we develop a state-and subject-specific functional network parcellation (the assignment of nodes to networks). Our parcellation approach provides a measure of how node-to-network assignment (NNA) changes across states and across subjects. We demonstrate that the brain’s functional networks are not spatially fixed, but reconfigure with brain state. This reconfiguration is robust and reliable to such an extent that it can be used to predict brain state with accuracies up to 97%.
A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts
Authors: Guyatt Anna L. , Brennan Rebecca R. , Burrows Kimberley , Guthrie Philip A. I. , Ascione Raimondo , Ring Susan , Gaunt Tom R. , Pyle Angela , Cordell Heather J. , Lawlor Debbie A. , Chinnery Patrick , Hudson Gavin , Rodriguez Santiago
Published: July 2018

Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist.

We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC), and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay), and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA, and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children, and UKBS males.

A neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], β[SE] −0.084 [0.016], p=1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, β[SE] 0.262 [0.034], p=1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N=11253), we replicated a published association in TFAM β[SE] 0.046 [0.017], p=0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS.

In a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN, and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.
Ventromedial prefrontal cortex is not critical for behavior change without external reinforcement
Authors: Aridan Nadav , Pelletier Gabriel , Fellows Lesley K , Schonberg Tom
Published: July 2018

Cue-approach training (CAT) is a novel paradigm that has been shown to induce preference changes towards items without external reinforcements. In the task the mere association of a neutral cue and a speeded button response has been shown to induce a behavioral change lasting months. This paradigm includes several phases whereby after the training of individual items, behavior change is manifested through binary choices of items with similar initial values. Neuroimaging data have implicated the ventromedial prefrontal cortex (vmPFC) during the choice phase of this task. However, it still remains unclear what are the underlying neural mechanisms during training. Here, we sought to determine whether the ventromedial frontal cortex (VMF) is critical for the non-reinforced preference change induced by CAT. For this purpose, eleven participants with focal lesions involving the VMF and 30 healthy age-matched controls performed the CAT. We found that at the individual level, a similar proportion of VMF and healthy participants showed a preference shift following CAT. The VMF group performed similarly to the healthy age-matched control group in the ranking and training phases. As a group the healthy age-matched controls exhibited a behavior change, but the VMF participants as a group did not. We did not find an association between individual lesion patterns and performance in the task. We conclude that a fully intact VMF is not critical to induce non-externally reinforced preference change and suggest potential mechanisms for this novel type of behavioral change.
The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain
Authors: Karolis VR , Corbetta M , Thiebaut de Schotten M
Published: July 2018

Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. We report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making, and that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere.
Large propulsion demands increase locomotor learning at the expense of step length symmetry
Authors: Sombric Carly J. , Calvert Jonathan S. , Torres-Oviedo Gelsy
Published: July 2018

There is a clinical interest in increasing the extent of locomotor learning induced by split-belt treadmills that move each leg at different speeds. However, factors facilitating locomotor learning are poorly understood. We hypothesized that augmenting the braking forces, rather than propulsion forces, experienced at the feet would increase locomotor adaptation and learning. To test this, forces were modulated during split-belt walking with distinct slopes: inclined (larger propulsion than braking), declined (larger braking than propulsion), and flat (similar propulsion and braking). These groups were compared using step length asymmetry, which is a clinically relevant measure robustly adapted on split-belt treadmills. Unexpectedly, the group with larger propulsion demands (i.e., the incline group) adapted faster and more, and had larger after-effects when the split-belt perturbation was removed. We also found that subjects who propelled more during baseline and experienced larger disruptions of propulsion forces in early adaptation exhibited greater after-effects, which further highlights the catalytic role of propulsion on locomotor learning. The relevance of mechanical demands on shaping our movements was also indicated by the steady state split-belt behavior, during which each group recovered their baseline leg orientation to meet leg-specific force demands at the expense of step length symmetry. Notably, the flat group was nearly symmetric, whereas the incline and decline group overshot and undershot symmetry, respectively. Taken together, our results indicate that forces propelling the body facilitate gait adaptation during split-belt walking. Therefore, interventions that increase propulsion demands may be a viable strategy for augmenting locomotor learning in individuals with hemiparesis.

Key Points Summary

Split-belt walking (i.e., legs moving at different speeds) can induce locomotor learning and even improve hemiparetic gait, but little is known about how to facilitate this process.

We investigated the effect of braking and propulsion forces on locomotor learning by testing young unimpaired subjects on the split-belt condition at different slopes (i.e., flat, decline, and incline), which distinctively modified these forces.

Propulsion forces facilitated locomotor learning indicated by 1) greater adaptation and after-effects following split-belt walking of the inclined group, which experienced larger propulsion demands and 2) a positive correlation between individual after-effects and subject-specific propulsion during regular walking and initial steps in the split condition.

Interestingly, incline and decline groups self-selected asymmetric step lengths at steady state in the split condition, challenging the prominent view that step length asymmetry is a biomarker for inefficient gait.

Our results suggest that interventions augmenting propulsion demands could correct hemiparetic gait more effectively.
Working-memory disruption by task-irrelevant talkers depends on degree of talker familiarity
Authors: Kreitewolf Jens , Wöstmann Malte , Tune Sarah , Plöchl Michael , Obleser Jonas
Published: July 2018

When listening, familiarity with an attended talker’s voice improves speech comprehension. Here, we instead investigated the effect of familiarity with a distracting talker. In an irrelevant-speech task, we assessed listeners’ working memory for the serial order of spoken digits when a task-irrelevant, distracting sentence was produced by either a familiar or an unfamiliar talker (with rare omissions of the task-irrelevant sentence). We tested two groups of listeners using the same experimental procedure. The first group were undergraduate psychology students (N=66) who had attended an introductory statistics course. Critically, each student had been taught by one of two course instructors, whose voices served as familiar and unfamiliar task-irrelevant talkers. The second group of listeners were family members and friends (N=20) who had known either one of the two talkers for more than ten years. Students, but not family members and friends, made more errors when the task-irrelevant talker was familiar versus unfamiliar. Interestingly, the effect of talker familiarity was not modulated by the presence of task-irrelevant speech: students experienced stronger working-memory disruption by a familiar talker irrespective of whether they heard a task-irrelevant sentence during memory retention or merely expected it. While previous work has shown that familiarity with an attended talker benefits speech comprehension, our findings indicate that familiarity with an ignored talker deteriorates working memory for target speech. The absence of this effect in family members and friends suggests that the degree of familiarity modulates memory disruption.
Requirements for efficient cotranscriptional regulatory switching in designed variants of the Bacillus subtilis pbuE adenine-responsive riboswitch
Authors: Drogalis Lea K. , Batey Robert T.
Published: July 2018

Riboswitches, generally located in the 5’-leader of bacterial mRNAs, direct expression via a small molecule-dependent structural switch informing the transcriptional or translational machinery. While the structure and function of riboswitch effector-binding (aptamer) domains have been intensely studied, only recently have the requirements for efficient linkage between small molecule binding and the structural switch in the cellular and cotranscriptional context begun to be actively explored. To address this, we have performed a structure-guided mutagenic analysis of the B. subtilis pbuE adenine-responsive riboswitch, one of the simplest riboswitches containing a secondary structural switch. Using a cell-based fluorescent protein reporter assay to assess ligand-dependent regulatory activity in E. coli, these studies revealed previously unrecognized features of the riboswitch. Most importantly, it was found that local and long-range conformational dynamics in two regions of the aptamer domain have a significant effect upon efficient regulatory switching. Further, sequence features of the expression platform including the pre-aptamer leader sequence, a nucleation helix and a putative programmed pause have clear affects upon ligand-dependent regulation. Together, these data point to sequence and structural features distributed throughout the riboswitch required to strike a balance between rates of ligand binding, transcription and secondary structural switching via a strand exchange mechanism.
Conservation and Variations of BimodalHoxDGene Regulation During Tetrapod Limb Development
Authors: Yakushiji-Kaminatsui Nayuta , Lopez-Delisle Lucille , Bolt Christopher Chase , Andrey Guillaume , Beccari Leonardo , Duboule Denis
Published: July 2018

In all tetrapods examined thus far, the development and patterning of limbs require the activation of gene members of theHoxDcluster. In mammals, they are controlled by a complex bimodal regulation, which controls first the proximal patterning, then the distal structure, allowing at the same time the formation of the wrist and ankle articulations. We analyzed the implementation of this regulatory mechanism in chicken, i.e. in an animal where large morphological differences exist between fore-and hindlimbs. We report that while this bimodal regulation is globally conserved between mammals and avian, some important modifications evolved at least between these two model systems, in particular regarding the activity of specific enhancers, the width of the TAD boundary separating the two regulations and the comparison between the forelimbversushindlimb regulatory controls. Some aspects of these regulations seem to be more conserved between chick and bats than with the mouse situation, which may relate to the extent to which forelimbs and hindlimbs of these various animals differ in their functions.

AUTHOR SUMMARY

The morphologies of limbs largely vary either amongst tetrapod species, or even between the fore-and hindlimbs of the same animal species. In order to try and evaluate whether variations in the complex regulation ofHoxdgenes during limb development may contribute to these differences, we compared their transcriptional controls during both fore-and hindlimb buds development in either the mouse, or the chicken embryos. We combined transcriptome analyses with 3D genome conformation, histone modification profiles and mouse genetics and found that the regulatory mechanism underlyingHoxdgene expression was highly conserved in all contexts, though with some clear differences. For instance, we observed a variation in the TAD boundary interval between the mouse and the chick, as well as differences in the activity of a conserved enhancer element (CS93) situated within the T-DOM regulatory landscape. In contrast to the mouse, the chicken enhancer indeed displayed a stronger activity in fore-than in hindlimb buds, coinciding with the observed striking differences in the mRNA levels. Altogether, differences in both the timing and duration of TAD activities and in the width of their boundary may parallel the important decrease inHoxdgene transcription in chick hindlimbversusforelimb buds. These differences may also account for the slightly distinct regulatory strategies implemented by mammals and birds at this locus, potentially leading to substantial morphological variations.
Assessing taxonomic metagenome profilers with OPAL
Authors: Meyer Fernando , Bremges Andreas , Belmann Peter , Janssen Stefan , McHardy Alice C. , Koslicki David
Published: July 2018

Taxonomic metagenome profilers predict the presence and relative abundance of microorganisms from shotgun sequence samples of DNA isolated directly from a microbial community. Over the past years, there has been an explosive growth of software and algorithms for this task, resulting in a need for more systematic comparisons of these methods based on relevant performance criteria. Here, we present OPAL, a software package implementing commonly used performance metrics, including those of the first challenge of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, OPAL implements diversity metrics from microbial ecology, as well as run time and memory efficiency measurements. By allowing users to customize the relative importance of metrics, OPAL facilitates in-depth performance comparisons, as well as the development of new methods and data analysis workflows. To demonstrate the application, we compared seven profilers on benchmark datasets of the first and second CAMI challenges using all metrics and performance measurements available in OPAL. The software is implemented in Python 3 and available under the Apache 2.0 license on GitHub (https://github.com/CAMI-challenge/OPAL).

Author summary

There are many computational approaches for inferring the presence and relative abundance of taxa (i.e. taxonomic profiling) from shotgun metagenome samples of microbial communities, making systematic performance evaluations a very important task. However, there has yet to be introduced a computational framework in which profiler performances can be compared. This delays method development and applied studies, as researchers need to implement their own custom evaluation frameworks. Here, we present OPAL, a software package that facilitates standardized comparisons of taxonomic metagenome profilers. It implements a variety of performance metrics frequently employed in microbiome research, including runtime and memory usage, and generates comparison reports and visualizations. OPAL thus facilitates and accelerates benchmarking of taxonomic profiling techniques on ground truth data. This enables researchers to arrive at informed decisions about which computational techniques to use for specific datasets and research questions.
Compensatory and additive helper effects in the cooperatively breeding Seychelles warbler (Acrocephalus sechellensis)
Authors: van Boheemen Lotte A. , Hammers Martijn , Kingma Sjouke A. , Richardson David S. , Burke Terry , Komdeur Jan , Dugdale Hannah L.
Published: July 2018

In cooperatively breeding species, helper aid may affect dominant breeders’ investment trade-offs between current and future reproduction. By compensating for the care provided by helpers, breeders can reduce the costs of reproduction and improve chances of survival. Also, helper care can be additive to that of dominants, resulting in higher success of the current brood.

However, the influence of helpers on offspring care itself may be the by-product of group size and territory quality. Therefore to make conclusive inferences about causation of additive and compensatory care as a result of helpper serequires disentangling the impact of helping from other factors determining parental investment.

In this study, we use 20 years of offspring provisioning data to investigate the effect of helping on breeder and overall offspring provisioning rates in the facultative cooperatively breeding Seychelles warbler (Acrocephalus sechellensis). Our extensive dataset allowed us to effectively control for the effects of living in a larger group and in territories with higher food availability.

We show compensatory and additive care in response to helper aid. Helpers lightened the provisioning load of the dominant male and female and increased the total provisioning to the nestlings. This was irrespective of group size or territory quality (food availability).

Our results illustrate how multiple benefits of helping behaviour can simultaneously be fundamental to the evolutionary maintenance of cooperative behaviour.
Diffusion of exit sites on the endoplasmic reticulum – a random walk on a shivering backbone
Authors: Stadler L. , Speckner K. , Weiss M.
Published: July 2018

Major parts of the endoplasmic reticulum (ER) in eukaryotic cells are organized as a dynamic network of membrane tubules connected by three-way junctions. On this network, self-assembled membrane domains, called ER exit sites (ERES), provide platforms at which nascent cargo proteins are packaged into vesicular carriers for subsequent transport along the secretory pathway. While ERES appear stationary and spatially confined on long time scales, we show here via single-particle tracking that they exhibit a microtubule-dependent anomalous diffusion behavior on short and intermediate time scales. By quantifying key parameters of their random walk, we show that the subdiffusive motion of ERES is distinct from that of ER junctions, i.e. ERES are not tied to junctions but rather are mobile on ER tubules. We complement and corroborate our experimental findings with model simulations that also indicate that ERES are not actively moved by microtubules. Altogether, our study shows that ERES perform a random walk on the shivering ER backbone, indirectly powered by microtubular activity. Similar phenomena can be expected for other domains on subcellular structures, setting a caveat for the interpretation of domain tracking data.
Plant resistance in different cell layers affects aphid probing and feeding behaviour during poor- and non-host interactions
Authors: Escudero-Martinez Carmen , Leybourne Daniel J. , Bos Jorunn I.B.
Published: July 2018

Aphids are phloem-feeding insects that cause economic losses to crops globally. Whilst aphid interactions with susceptible plants and partially resistant genotypes have been well characterised with regards to aphid probing and feeding behaviour, the interactions with non-natural host species are not well understood. Using aphid choice assays with the broad host range pest Myzus persicae and the cereal pest Rhopalosiphum padi we show that about 10% of aphids settle on non-/poor-host species over a 24h time period. We used the Electrical Penetration Graph technique to assess aphid probing and feeding behaviour during the non-/poor-host interactions. In the Arabidopsis non-host interaction with the cereal pest R. padi aphids were unable to reach and feed from the phloem, with resistance likely residing in the mesophyll cell layer. In the barley poor-host interaction with M. persicae, resistance is likely phloem-based as aphids were able to reach the phloem but ingestion was reduced compared with the host interaction. Overall our data suggests that plant resistance to aphids in non-host and poor-host interactions with these aphid species likely resides in different plant cell layers. Future work will take into account specific cell layers where resistances are based to dissect the underlying mechanisms and gain a better understanding of how we may improve crop resistance to aphids.
Drought adaptation in nature by extensive genetic loss-of-function
Authors: Monroe J.G. , Powell T. , Price N. , Mullen J.L. , Howard A. , Evans K. , Lovell J.T. , McKay J.K.
Published: July 2018

Visions of a second green revolution empowered by emerging technologies have called for interdisciplinary syntheses to scale up the discovery of functionally definitive gene variants responsible for climate adaptation in plants. We integrated novel approaches using whole genome sequences and satellite remote sensing to identify natural knockout alleles associated with drought histories in wild Arabidopsis thaliana. Genes identified exhibit signatures of parallel molecular evolution, selection for loss-of-function alleles, and shared associations with flowering time phenotypes in directions consistent with longstanding adaptive hypotheses 7 times more often than expected by chance. Artificial knockout lines then confirmed predicted phenotypes experimentally. These findings further challenge popular assumptions about the adaptive value of genetic loss-of-function in nature and inspire new opportunities for engineering climate resilience in crops.

One sentence summary

Whole genome sequences and satellite-detected droughts point to gene knockouts as valuable genetic fuel for climate adaptation.
Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice
Authors: Bacon Wendi A. , Hamilton Russell S. , Yu Ziyi , Kieckbusch Jens , Hawkes Delia , Krzak Ada M. , Abell Chris , Colucci Francesco , Charnock-Jones D. Stephen
Published: July 2018

Fetal growth restriction (FGR) causes a wide variety of defects in the neonate which can lead to increased risk of heart disease, diabetes, anxiety and other disorders later in life. However, the effect of FGR on the immune system, is poorly understood. We used a well-characterized mouse model of FGR in which placental Igf-2 production is lost due to deletion of the placental specificIgf-2P0promotor. The thymi in such animals were reduced in mass with a ∼70% reduction in cellularity. We used single cell RNA sequencing (Drop-Seq) to analyze 7264 thymus cells collected at postnatal day 6.

We identified considerable heterogeneity among the Cd8/Cd4 double positive cells with one subcluster showing marked upregulation of transcripts encoding a sub-set of proteins that contribute to the surface of the ribosome. The cells from the FGR animals were underrepresented in this cluster. Furthermore, the distribution of cells from the FGR animals was skewed with a higher proportion of immature double negative cells and fewer mature T-cells. Cell cycle regulator transcripts also varied across clusters. The T-cell deficit in FGR mice persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This finding complements the altered immunity found in growth restricted human infants. This reduction in T-cellularity may have implications for adult immunity, adding to the list of adult conditions in which thein uteroenvironment is a contributory factor.
Demand for pesticide-free, cisgenic food? Exploring differences between consumers of organic and conventional food
Authors: Edenbrandt Anna Kristina
Published: July 2018

Purpose

The purpose of this paper is to explore the consumer acceptance of foods that are pesticide-free while obtained by cisgenics, a form of genetic modification that only allows gene transfers between sexually compatible species. Potential differences in acceptance between conventional and organic consumer segments are explored.

Design/methodology/approach

Data were collected from a survey, including a choice experiment, which was distributed to a consumer panel in Denmark. Survey responses were combined with actual purchase data among the same respondents and thereby providing information about the respondents’ share of organic consumption.

Findings

No consumer segment differentiated between pesticide-free, cisgenic bread and conventional alternatives. Conventional consumers preferred cisgenics over transgenics, while pesticide-free is not highly valued. Frequent organic consumers were having willingness-to-pay (WTP) a large premium for organic, indicating that they will continue to purchase such products even if cisgenic, pesticide-free products are introduced.

Originality/value

This paper provides insights on the potential reception of cisgenic food, and if there is a positive willingness to pay for a pesticide-free label if this is cisgenics. Moreover, the possibility to allow new breeding techniques in the organic requirements has been discussed, and this paper contributes with insights on the organic consumers’ preferences on this matter.
Australian food retail supply chain analysis
Authors: Jie Ferry , Gengatharen Denise
Published: July 2018

Purpose

The Australian retail food sector, comprising mostly small enterprises, is undergoing change as a result of the innovative supply chain approach adopted. This change has implications across the entire food value chain in Australia. The purpose of this paper is to empirically investigate the adoption of supply chain management practices on small and medium enterprises (SMEs) in the Australian food retail industry.

Design/methodology/approach

The study surveys 120 SME retailers in the food sector. A stepwise multiple regression using SPSS version 14.0 was performed on the data.

Findings

Statistical results suggest that lean thinking and the quality of information shared can lead to greater efficient supply chain performance.

Research limitations/implications

The small sample is the main limitation. The findings bear important implications for further research as understanding these dimensions can help to position key changes and industry improvement that will increase revenue and reduce cost to the SMEs in the food retail supply chain.

Practical implications

Adopting lean thinking and improving information sharing in the supply chain can reduce the cost for SMEs.

Social implications

This study has unique implications for social sustainability, especially the smaller food enterprises, which are hard pressed to combat the challenges within the food sector.

Originality/value

Innovative supply chain management helps SMEs to see beyond the silo mentality and helps them to focus on greater value addition in the supply chain.
Business process orientation in the Slovenian power supply
Authors: Novak Rajko , Janeš Aleksander
Published: July 2018

Purpose

The purpose of this paper is to empirically evaluate business process orientation (BPO) of the Slovenian power supply business.

Design/methodology/approach

Within the empirical investigation, the level of BPO maturity was measured in the 19 organizations of the power supply business. The survey was focused on the top, middle and lower managers. As a measuring instrument, a questionnaire for the extended concept of process orientation with nine elements was used.

Findings

The results of the BPO measurement show that, despite this long-standing preoccupation with processes, certified management system and the computerization of operations, process maturity is not high. Particularly the lowest score for information technology represents a surprise.

Practical implications

This research makes significant contributions to the literature and above all to scholars and practitioners who work professionally in this field and will find useful guidance for a better understanding of applying BPO and maturity models.

Social implications

One important reason for performing the maturity measurement in the power supply business is the importance of its activities for the operation and development and environmental impact of the whole of Slovenian society.

Originality/value

Presented research is the first one which considers the BPO maturity in the Slovenian power supply business and therefore contributes to understanding of the “intangible factors” which have impact on the introduction of business process management and BPO.