bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative Evaluation Is Not Predictive of Transpyloric Feeding Conversion in Gastrostomy‐dependent Pediatric Patients
Authors: McSweeney Maireade E. , Kerr Jessica , Amirault Janine , Fishman Eliza , Lurie Margot , Peinado‐Fabregat Maria I. , Mitchell Paul D. , Rosen Rachel
Published: December 2017

Objectives:

Limited literature exists as to whether preoperative gastrostomy (GT) evaluation may predict which patients will go onto require gastrojejunostomy (GJ) tube feeding. The goal of this study was to compare the preoperative evaluations between patients maintained on GT feeds versus patients who required conversion to GJ feeds.

Methods:

We identified patients at Boston Children's Hospital who underwent GT tube placement and required GJ feeding between 2006 and 2012. GT patients were matched according to age, neurologic, and cardiac status with GJ‐converted patients. Preoperative characteristics, rates of total hospitalizations, and respiratory‐related admissions were reviewed.

Results:

A total of 79 GJ patients (median interquartile range (IQR): age 15 (4.3, 55.7) months; weight 8.8 (4.6, 14.5) kg) were matched with 79 GT patients (median (IQR): age 14.6 (4.7, 55.7) months; weight 8.5 (5, 13.6) kg). Median time from GT to GJ conversion was 8 (IQR 3, 16) months. Both groups had similar rates of successful preoperative nasogastric feeding trials (GT (84.5%) versus GJ (83.1%), P = 1.0), upper gastrointestinal series (GT (89.1%) versus GJ (93.2%), P = 0.73), abnormal videofluoroscopic swallow studies (GT (53.8%) versus GJ (62.2%), P = 0.4), and completion of gastric emptying studies (GT (10.1%) versus GJ (5.1%), P = 0.22). No differences were seen in preoperative hospitalization rates (P = 0.25), respiratory admissions (P = 0.36), although GJ patients had a mean reduction in the number of hospitalization of −1.5 ± 0.5 days, P < 0.001, after conversion.

Conclusions:

No differences in preoperative patient characteristics or diagnostic evaluations were seen in GT fed versus GJ converted patients. GJ patients did experience an overall decrease in total admissions after GJ conversion.
Airway Volume Simulation in Virtual Mandibular Distraction: A Cohort Study
Authors: Humphries Laura S. , Yates Essie K. , Mhlaba Julie M. , Collins John M. , Baroody Fuad M. , Reid Russell R.
Published: December 2017

Background:

The authors investigated the accuracy of virtual surgical planning in predicting airway volume changes after mandibular distraction in patients with Pierre Robin sequence and associated tongue-based airway obstruction.

Methods:

The authors completed a single-institution retrospective review of patients for whom virtual surgical planning was used during mandibular distraction osteogenesis for treatment of tongue-based airway obstruction. Preoperative airway volume, virtual surgical planning–predicted airway volume, and postoperative airway volume were calculated from three-dimensional computed tomographic scans using industry software. A blinded institutional radiologist also calculated pre- and post-operative airway volumes. Pre- and post-operative polysomnography was used to titrate the endpoint of mandibular lengthening.

Results:

Eleven patients were included in the study. Mean apnea-hypopnea index (5.42 ± 4.53 versus 44.96 ± 20.57;p< 0.001) and mean nadir oxygen saturation (70.3 ± 9.72 percent versus 82.9 ± 9.62 percent;p= 0.003) improved with mandibular distraction. There was moderate correlation between predicted and actual mandibular distraction lengths (R2= 0.65;p= 0.003). There was a strong correlation between predicted and industry-calculated actual post–distraction airway volume (R2= 0.99;p< 0.001). There was no significant correlation between actual mandibular distraction length and industry-calculated actual post–distraction airway volume for the entire cohort (R2= 0.05;p= 0.49), but correlation approached significance by institutional calculations. No significant correlation existed between industry and institutional-calculated percentage change in post–distraction airway volume (R2= 0.06;p= 0.57).

Conclusions:

Predictive airway volume calculation may be an effective adjunct to determine anatomic endpoint of mandibular distraction but small sample size, operator and software variability, and patient airway morphology may confound firm conclusions. Further studies are warranted.
Apathy and Cognitive Deficits in Patients with Transient Global Ischemia After Cardiac Arrest
Authors: Frisch Stefan , Thiel Friederike , Schroeter Matthias L. , Jentzsch Regina Tina
Published: December 2017

Background and Objective:

Despite the extensive literature on cognitive deficits in the course of transient global ischemia after cardiac arrest with delayed resuscitation, apathy has been studied less frequently and systematically. We aimed to evaluate the frequency of apathy, defined as changes in drive or lack of motivation, and its relation to cognition as well as depression in people with transient global ischemia after cardiac arrest.

Methods:

In a retrospective study using the clinical data of 38 cardiac arrest survivors, we analyzed the frequency and severity of deficits in four cognitive domains (attention, memory spans, long-term memory, and executive functions) as well as apathy.

Results:

As in previous studies, long-term memory problems were predominant, but occurred rarely in isolation. Problems in drive were frequent and correlated with the severity of deficits in all cognitive domains except memory spans (and executive functions only as a trend). Influences of apathy were independent of the presence of a depressive syndrome.

Conclusions:

Transient global ischemia after cardiac arrest generally leads to a broad pattern of cognitive decline with predominating memory deficits. Apathy is a frequent sequela and is associated with cognitive deficits, independent of depression. Studies investigating the cognitive profile after cardiac arrest should account for modulating influences of apathy.
Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation
Authors: Harvey Denise Y. , Podell Jamie , Turkeltaub Peter E. , Faseyitan Olufunsho , Coslett H. Branch , Hamilton Roy H.
Published: December 2017

Background and Objective:

While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation.

Methods:

Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS.

Results:

Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased.

Conclusions:

This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally.

Clinical Trial Registration:

ClinicalTrials.gov (Identifier NCT00608582).
Advances in the relationship between Kruppel-like factor 15 and cardiovascular disease research
Authors: Yuping Yang , Hua Chen , Qing Zhou
Published: December 2017

Kruppel-like factor 15 (KLF15) is a subtype of the Kruppel-like family of transcription factors (KLFs). KLFs have three high-fidelity zinc fingers at the carboxyl terminus that enable them to regulate the biological processes of proliferation, differentiation, cellular development, and apoptosis. KLF15 is highly expressed in the kidney, pancreas, and cardiac and skeletal muscle, and plays an essential role in the development and occurrence of multiple system diseases. In this paper, we underscored the important relationship between KLF15 and cardiovascular diseases such as atherosclerosis, heart failure, arrhythmia, aortic lesions, etc. On this basis, we identified KLF15 as a potential therapeutic target for the treatment of cardiovascular disease.
A review of active hot-spring analogues of Rhynie: environments, habitats and ecosystems
Authors: Channing Alan
Published: December 2017

The Lower Devonian Rhynie chert formed as silica sinter entombed an early terrestrial ecosystem. Silica sinter precipitates only from water flowing from alkali-chloride hot springs and geysers, the surface expression of crustal-scale geothermal systems that form low-sulfidation mineral deposits in the shallow subsurface. Active alkali-chloride hot springs at Yellowstone National Park create a suite of geothermally influenced environments; vent pools, sinter aprons, run-off streams, supra-apron terrace pools and geothermal wetlands that are habitats for modern hot-spring ecosystems. The plant-rich chert, which makes Rhynie internationally famous, probably formed in low-temperature environments at the margins of a sinter apron where frequent flooding by geothermal water and less frequent flooding by river waters created ephemeral to permanent wetland conditions. Here, the plants and associated microbes and animals would be immersed in waters with elevated temperature, brackish salinity, high pH and a cocktail of phytotoxic elements which created stresses that the fossil ecosystem must have tolerated. The environment excluded coeval mesophytic plants, creating a low-diversity hot-spring flora. Comparison with Yellowstone suggests the Rhynie plants were preadapted to their environment by life in more common and widespread environments with elevated salinity and pH such as coastal marshes, salt lakes, estuaries and saline seeps.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Palaeoecology and palaeophytogeography of the Rhynie chert plants: further evidence from integrated analysis ofin situand dispersed spores
Authors: Wellman Charles H.
Published: December 2017

The remarkably preserved Rhynie chert plants remain pivotal to our understanding of early land plants. The extraordinary anatomical detail they preserve is a consequence of exceptional preservation, by silicification, in the hot-springs environment they inhabited. However, this has prompted questions as to just how typical of early land plants the Rhynie chert plants really are. Some have suggested that they were highly adapted to the unusual hot-springs environment and are unrepresentative of ‘normal’ plants of the regional flora. New quantitative analysis of dispersed spore assemblages from the stratigraphical sequence of the Rhynie outlier, coupled with characterization of thein situspores of the Rhynie chert plants, permits investigation of their palaeoecology and palaeophytogeography. It is shown that the Rhynie inland intermontane basin harboured a relatively diverse flora with only a small proportion of these plants actually inhabiting the hot-springs environment. However, the flora of the Rhynie basin differed from coeval lowland floodplain deposits on the same continent, as it was less diverse, lacked some important spore groups and contained some unique elements. At least some of the Rhynie plants (e.g.Horneophyton lignieri) existed outside the hot-springs environment, inhabiting the wider basin, and were indeed palaeogeographically widespread. They probably existed in the hot-springs environment because they were preadapted to this unstable and harsh setting.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Antheridial development in the moss
Physcomitrella patens
: implications for understanding stem cells in mosses
Authors: Kofuji Rumiko , Yagita Yasushi , Murata Takashi , Hasebe Mitsuyasu
Published: December 2017

Stem cells self-renew and produce precursor cells that differentiate to become specialized cell types. Land plants generate several types of stem cells that give rise to most organs of the plant body and whose characters determine the body organization. The moss
Physcomitrella patens
forms eight types of stem cells throughout its life cycle. Under gametangium-inducing conditions, multiple antheridium apical stem cells are formed at the tip of the gametophore and each antheridium apical stem cell divides to form an antheridium. We found that the gametophore apical stem cell, which typically forms leaf and stem tissues, changes to become a new type of stem cell, which we term the antheridium initial stem cell. This antheridium initial stem cell produces multiple antheridium apical stem cells, resulting in a cluster of antheridia at the tip of gametophore. This is the first report of a land plant stem cell directly producing another type of stem cell during normal development. Notably, the antheridium apical stem cells are distally produced from the antheridium initial stem cell, similar to the root cap stem cells of vascular plants, suggesting the use of similar molecular mechanisms and a possible evolutionary relationship.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
The origin and early evolution of vascular plant shoots and leaves
Authors: Harrison C. Jill , Morris Jennifer L.
Published: December 2017

The morphology of plant fossils from the Rhynie chert has generated longstanding questions about vascular plant shoot and leaf evolution, for instance, which morphologies were ancestral within land plants, when did vascular plants first arise and did leaves have multiple evolutionary origins? Recent advances combining insights from molecular phylogeny, palaeobotany and evo–devo research address these questions and suggest the sequence of morphological innovation during vascular plant shoot and leaf evolution. The evidence pinpoints testable developmental and genetic hypotheses relating to the origin of branching and indeterminate shoot architectures prior to the evolution of leaves, and demonstrates underestimation of polyphyly in the evolution of leaves from branching forms in ‘telome theory’ hypotheses of leaf evolution. This review discusses fossil, developmental and genetic evidence relating to the evolution of vascular plant shoots and leaves in a phylogenetic framework.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
The evolution of the stomatal apparatus: intercellular spaces and sporophyte water relations in bryophytes—two ignored dimensions
Authors: Duckett Jeffrey G. , Pressel Silvia
Published: December 2017

Cryo-scanning electron microscopy shows that nascent intercellular spaces (ICSs) in bryophytes are liquid-filled, whereas these are gas-filled from the outset in tracheophytes except in the gametophytes of Lycopodiales. ICSs are absent in moss gametophytes and remain liquid-filled in hornwort gametophytes and in both generations in liverworts. Liquid is replaced by gas following stomatal opening in hornworts and is ubiquitous in moss sporophytes even in astomate taxa. New data on moss water relations and sporophyte weights indicate that the latter are homiohydric while X-ray microanalysis reveals an absence of potassium pumps in the stomatal apparatus. The distribution of ICSs in bryophytes is strongly indicative of very ancient multiple origins. Inherent in this scenario is either the dual or triple evolution of stomata. The absence, in mosses, of any relationship between increases in sporophyte biomass and stomata numbers and absences, suggests that CO
2
entry through the stomata, possible only after fluid replacement by gas in the ICSs, makes but a minor contribution to sporophyte nutrition. Save for a single claim of active regulation of aperture dimensions in mosses, all other functional and structural data point to the sporophyte desiccation, leading to spore discharge, as the primeval role of the stomatal apparatus.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Bilaterally symmetric axes with rhizoids composed the rooting structure of the common ancestor of vascular plants
Authors: Hetherington Alexander J. , Dolan Liam
Published: December 2017

There are two general types of rooting systems in extant land plants: gametophyte rhizoids and sporophyte root axes. These structures carry out the rooting function in the free-living stage of almost all land plant gametophytes and sporophytes, respectively. Extant vascular plants develop a dominant, free-living sporophyte on which roots form, with the exception of a small number of taxa that have secondarily lost roots. However, fossil evidence indicates that early vascular plants did not develop sporophyte roots. We propose that the common ancestor of vascular plants developed a unique rooting system—rhizoidal sporophyte axes. Here we present a synthesis and reinterpretation of the rootless sporophytes ofHorneophyton lignieri,Aglaophyton majus,Rhynia gwynne-vaughaniiandNothia aphyllapreserved in the Rhynie chert. We show that the sporophyte rooting structures of all four plants comprised regions of plagiotropic (horizontal) axes that developed unicellular rhizoids on their underside. These regions of axes with rhizoids developed bilateral symmetry making them distinct from the other regions which were radially symmetrical. We hypothesize that rhizoidal sporophyte axes constituted the rooting structures in the common ancestor of vascular plants because the phylogenetic positions of these plants span the origin of the vascular lineage.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
FertilePrototaxites taiti: a basal ascomycete with inoperculate, polysporous asci lacking croziers
Authors: Honegger Rosmarie , Edwards Dianne , Axe Lindsey , Strullu-Derrien Christine
Published: December 2017

The affinities ofPrototaxiteshave been debated ever since its fossils, some attaining tree-trunk proportions, were discovered in Canadian Lower Devonian rocks in 1859. Putative assignations include conifers, red and brown algae, liverworts and fungi (some lichenised). Detailed anatomical investigation led to the reconstruction of the type species,P. logani, as a giant sporophore (basidioma) of an agaricomycete (= holobasidiomycete), but evidence for its reproduction remained elusive. Tissues associated withP. taitiin the Rhynie chert plus charcoalified fragments from southern Britain are investigated here to describe the reproductive characters and hence affinities ofPrototaxites. Thin sections and peels (Pragian Rhynie chert, Aberdeenshire) were examined using light and confocal microscopy; Přídolí and Lochkovian charcoalified samples (Welsh Borderland) were liberated from the rock and examined with scanning electron microscopy.Prototaxites taitipossessed a superficial hymenium comprising an epihymenial layer, delicate septate paraphyses, inoperculate polysporic asci lacking croziers and a subhymenial layer composed predominantly of thin-walled hyphae and occasional larger hyphae.Prototaxites taiticombines features of extant Taphrinomycotina (Neolectomycetes lacking croziers) and Pezizomycotina (epihymenial layer secreted by paraphyses) but is not an ancestor of the latter. Brief consideration is given to its nutrition and potential position in the phylogeny of the Ascomycota.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Changing expressions: a hypothesis for the origin of the vascular plant life cycle
Authors: Kenrick Paul
Published: December 2017

Plant life cycles underwent fundamental changes during the initial colonization of the land in the Early Palaeozoic, shaping the direction of evolution. Fossils reveal unanticipated diversity, including new variants of meiotic cell division and leafless gametophytes with mycorrhizal-like symbioses, rhizoids, vascular tissues and stomata. Exceptional fossils from the 407-Ma Rhynie chert (Scotland) play a key role in unlocking this diversity. These fossils are reviewed against progress in our understanding of the plant tree of life and recent advances in developmental genetics. Combining data from different sources sheds light on a switch in life cycle that gave rise to the vascular plants. One crucial step was the establishment of a free-living sporophyte from one that was an obligate matrotroph borne on the gametophyte. It is proposed that this difficult evolutionary transition was achieved through expansion of gene expression primarily from the gametophyte to the sporophyte, establishing a now extinct life cycle variant that was more isomorphic than heteromorphic. These changes also linked for the first time in one developmental system rhizoids, vascular tissues and stomata, putting in place the critical components that regulate transpiration and forming a physiological platform of primary importance to the diversification of vascular plants.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Optimal cross selection for long-term genetic gain in two-part programs with rapid recurrent genomic selection
Authors: Gorjanc Gregor , Gaynor R. Chris , Hickey John M.
Published: December 2017

This study evaluates optimal cross selection for balancing selection and maintenance of genetic diversity in two-part plant breeding programs with rapid recurrent genomic selection. The two-part program reorganizes a conventional breeding program into population improvement component with recurrent genomic selection to increase the mean of germplasm and product development component with standard methods to develop new lines. Rapid recurrent genomic selection has a large potential, but is challenging due to genotyping costs or genetic drift. Here we simulate a wheat breeding program for 20 years and compare optimal cross selection against truncation selection in the population improvement with one to six cycles per year. With truncation selection we crossed a small or a large number of parents. With optimal cross selection we jointly optimised selection, maintenance of genetic diversity, and cross allocation with AlphaMate program. The results show that the two-part program with optimal cross selection delivered the largest genetic gain that increased with the increasing number of cycles. With four cycles per year optimal cross selection had 78% (15%) higher long-term genetic gain than truncation selection with a small (large) number of parents. Higher genetic gain was achieved through higher efficiency of converting genetic diversity into genetic gain; optimal cross selection quadrupled (doubled) efficiency of truncation selection with a small (large) number of parents. Optimal cross selection also reduced the drop of genomic selection accuracy due to the drift between training and prediction populations. In conclusion, optimal cross-selection enables optimal management and exploitation of population improvement germplasm in two-part programs.

Key message

Optimal cross selection increases long-term genetic gain of two-part programs with rapid recurrent genomic selection. It achieves this by optimising efficiency of converting genetic diversity into genetic gain through reducing the loss of genetic diversity and reducing the drop of genomic prediction accuracy with rapid cycling.
Sex-specific genome-wide association study in glioma identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
Authors: Ostrom Quinn T. , Kinnersley Ben , Wrensch Margaret R. , Eckel-Passow Jeanette E. , Armstrong Georgina , Rice Terri , Chen Yanwen , Wiencke John K. , McCoy Lucie S. , Hansen Helen M. , Amos Christopher I. , Bernstein Jonine L. , Claus Elizabeth B. , Il’yasova Dora , Johansen Christoffer , Lachance Daniel H. , Lai Rose K. , Merrell Ryan T. , Olson Sara H. , Sadetzki Siegel , Schildkraut Joellen M. , Shete Sanjay , Rubin Joshua B. , Lathia Justin D. , Berens Michael E. , Andersson Ulrika , Rajaraman Preetha , Chanock Stephen J. , Linet Martha S. , Wang Zhaoming , Linet Martha S. , Wang Zhaoming , Yeager Meredith ,   on behalf of the GliomaScan consortium, Houlston Richard S. , Jenkins Robert B. , Melin Beatrice , Bondy Melissa L. , Barnholtz-Sloan Jill. S.
Published: December 2017

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
Long-read sequencing of nascent RNA reveals coupling among RNA processing events
Authors: Herzel Lydia , Straube Korinna , Neugebauer Karla M.
Published: December 2017

Pre-mRNA splicing is accomplished by the spliceosome, a megadalton complex that assembles de novo on each intron. Because spliceosome assembly and catalysis occur co-transcriptionally, we hypothesized that introns are removed in the order of their transcription in genomes dominated by constitutive splicing. Remarkably little is known about splicing order and the regulatory potential of nascent transcript remodeling by splicing, due to the limitations of existing methods that focus on analysis of mature splicing products (mRNAs) rather than substrates and intermediates. Here, we overcome this obstacle through long-read RNA sequencing of nascent, multi-intron transcripts in the fission yeast Schizosaccharomyces pombe. Most multi-intron transcripts were fully spliced, consistent with rapid co-transcriptional splicing. However, an unexpectedly high proportion of transcripts were either fully spliced or fully unspliced, suggesting that splicing of any given intron is dependent on the splicing status of other introns in the transcript. Supporting this, mild inhibition of splicing by a temperature-sensitive mutation in Prp2, the homolog of vertebrate U2AF65, increased the frequency of fully unspliced transcripts. Importantly, fully unspliced transcripts displayed transcriptional read-through at the polyA site and were degraded co-transcriptionally by the nuclear exosome. Finally, we show that cellular mRNA levels were reduced in genes with a high number of unspliced nascent transcripts during caffeine treatment, showing regulatory significance of co-transcriptional splicing. Therefore, overall splicing of individual nascent transcripts, 3’ end formation, and mRNA half-life depend on the splicing status of neighboring introns, suggesting crosstalk among spliceosomes and the polyA cleavage machinery during transcription elongation.
Molecular data from Orthonectid worms show they are highly degenerate members of phylum Annelida not phylum Mesozoa
Authors: Schiffer Philipp H. , Robertson Helen E. , Telford Maximilian J.
Published: December 2017

The Mesozoa are a group of tiny, extremely simple, vermiform endoparasites of various marine animals (Fig. 1). There are two recognised groups within the Mesozoa: the Orthonectida (Fig. 1a,b; with a few hundred cells including a nervous system made up of just 10 cells [1]) and the Dicyemids (Fig. 1c; with at most 42 cells [2]). They are classic ‘Problematica’ [3] - the name Mesozoa suggests an evolutionary position intermediate between Protozoa and Metazoa (animals) [4] and implies their simplicity is a primitive state, but molecular data have shown they are members of Lophotrochozoa within Bilateria [5-8] which would mean they derive from a more complex ancestor. Their precise phylogenetic affinities remain uncertain, however, and ascertaining this is complicated by the very fast evolution observed in genes from both groups, leading to the common systematic error of Long Branch Attraction (LBA) [9]. Here we use mitochondrial and nuclear gene sequence data, and show beyond doubt that both dicyemids and orthonectids are members of the Lophotrochozoa. Carefully addressing the effects of systematic errors due to unequal rates of evolution, we show that the phylum Mesozoa is polyphyletic. While the precise position of dicyemids remains unresolved within Lophotrochozoa, we unequivocally identify orthonectids as members of the phylum Annelida. This result reveals one of the most extreme cases of body plan simplification in the animal kingdom; our finding makes sense of an annelid-like cuticle in orthonectids [1] and suggests the circular muscle cells repeated along their body [10] may be segmental in origin.
Deep generative models of genetic variation capture mutation effects
Authors: Riesselman Adam J. , Ingraham John B. , Marks Debora S.
Published: December 2017

The functions of proteins and RNAs are determined by a myriad of interactions between their constituent residues, but most quantitative models of how molecular phenotype depends on genotype must approximate this by simple additive effects. While recent models have relaxed this constraint to also account for pairwise interactions, these approaches do not provide a tractable path towards modeling higher-order dependencies. Here, we show how latent variable models with nonlinear dependencies can be applied to capture beyond-pairwise constraints in biomolecules. We present a new probabilistic model for sequence families, DeepSequence, that can predict the effects of mutations across a variety of deep mutational scanning experiments significantly better than site independent or pairwise models that are based on the same evolutionary data. The model, learned in an unsupervised manner solely from sequence information, is grounded with biologically motivated priors, reveals latent organization of sequence families, and can be used to extrapolate to new parts of sequence space.
Biodiversity loss under future global socio-economic and climate scenarios
Authors: Chaudhary Abhishek , Mooers Arne O.
Published: December 2017

Efficient forward-looking mitigation measures are needed to halt the global biodiversity decline. These require spatially explicit scenarios of expected changes in multiple indicators of biodiversity under future socio-economic and environmental conditions. Here we link five future (2050 and 2100) global gridded maps (0.25° × 0.25° resolution) available from the land use harmonization (LUH) database that represent alternative representative concentration and shared socio-economic pathways (RCP-SSP) with the countryside species-area relationship model to project the future land use change driven rates of species extinctions and phylogenetic diversity loss (in million years) for mammals, birds and amphibians in each of the 804 terrestrial ecoregions and 176 countries and compare them to the current (1900-2015) and past (850-1900) rates of biodiversity loss. Future land-use changes are projected to commit an additional 209-818 endemic species and 1190-4402 million years of evolutionary history to extinction by 2100 depending upon the scenario, equivalent to 20–80% of the number committed to extinction under current (2015) land use extent. Results show that hotspots of future biodiversity loss differ depending upon the scenario, taxon and metric considered. The most aggressive climate mitigation scenario (RCP2.6 SSP-1), representing a world shifting towards a radically more sustainable path including increasing crop yields, reduced meat production and reduced tropical deforestation coupled with high trade, projects the lowest land use change driven global biodiversity loss followed by RCP8.5 SSP-5, RCP6.0 SSP-4 and RCP7.0 SSP-3. Interestingly, the scenario with the second most aggressive climate target (RCP3.4 SSP-4) projected the highest biodiversity loss among the five scenarios tested. This is because it represents a world with continued high consumption in rich countries and increased land clearing for crop production in species rich, low-income countries such as Indonesia, Madagascar, Tanzania, Philippines and DR Congo. These contrasting results illustrate that the strategies to prevent climate change could simultaneously contribute to reduction in current high rates of biodiversity loss, but only if habitat preservation is incorporated into national and global sustainable development plans.
Multivariate genotypic analyses that identify specific genotypes to characterize disease and control groups in ADNI
Authors: Beaton Derek , Rieck Jenny R. , Alhazmi Fahd ,   ADNI, Abdi Hervé
Published: December 2017

INTRODUCTION

Genetic contributions to Alzheimer’s Disease (AD) are likely polygenic and not necessarily explained by uniformly applied linear and additive effects. In order to better understand the genetics of AD, we require statistical techniques to address both polygenic and possible non-additive effects.

METHODS

We used partial least squares-correspondence analysis (PLS-CA)—a method designed to detect multivariate genotypic effects. We used ADNI-1 (N = 756) as a discovery sample with two forms of PLS-CA: diagnosis-based and ApoE-based. We used ADNI-2 (N= 791) as a validation sample with a diagnosis-based PLS-CA.

RESULTS

With PLS-CA we identified some expected genotypic effects (e.g., APOE/TOMM40, and APP) and a number of new effects that include, for examples, risk-associated genotypes in RBFOX1 and GPC6 and control-associated genotypes in PTPN14 and CPNE5.

DISCUSSION

Through the use of PLS-CA, we were able to detect complex (multivariate, genotypic) genetic contributions to AD, which included many non-additive and non-linear risk and possibly protective effects.
Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact
Authors: Ray Thomas A. , Roy Suva , Kozlowski Christopher , Wang Jingjing , Cafaro Jon , Hulbert Samuel W. , Wright Christopher V. , Field Greg D. , Kay Jeremy N.
Published: December 2017

Impact statement

Selective synapse formation in a retinal motion-sensitive circuit is orchestrated by starburst amacrine cells, which use homotypic interactions to initiate formation of a dendritic scaffold that recruits projections from circuit partners.

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers.
Characterisation of two Toxoplasma PROPPINs homologous to Atg18/WIPI suggests they have evolved distinct specialised functions
Authors: Nguyen Hoa Mai , Liu Shuxian , Daher Wassim , Tan Feng , Besteiro Sébastien
Published: December 2017

Toxoplasma gondii is a parasitic protist possessing a limited set of proteins involved in the autophagy pathway, a self-degradative machinery for protein and organelle recycling. This distant eukaryote has even repurposed part of this machinery, centered on protein ATG8, for a non-degradative function related to the maintenance of the apicoplast, a parasite-specific organelle. However, some evidence also suggest Toxoplasma is able to generate autophagic vesicles upon stress, and that some autophagy-related proteins, such as ATG9, might be involved solely in the canonical autophagy function. Here, we have characterised two Toxoplasma proteins containing WD-40 repeat that can bind lipids for their recruitment to vesicular structures upon stress. They belong to the PROPPIN family and are homologues to ATG18/WIPI, which are known to be important for the autophagic process. We conducted a functional analysis of these two Toxoplasma PROPPINs. One of them is dispensable for normal in vitro growth, although it may play a role for parasite survival in specific stress conditions or for parasite fitness in the host, through a canonical autophagy-related function. The other, however, seems important for parasite viability in normal growth conditions and could be primarily involved in a non-canonical function. These divergent roles for two proteins from the same family illustrate the functional versatility of the autophagy-related machinery in Toxoplasma.
Fibroblast state switching orchestrates dermal maturation and wound healing
Authors: Rognoni Emanuel , Pisco Angela Oliveira , Hiratsuka Toru , Sipilä Kalle , Belmonte Julio M. , Mobasseri Seyedeh Atefeh , Philippeos Christina , Dilão Rui , Watt Fiona M.
Published: December 2017

Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.

Standfirst text

We show that fibroblast behaviour switching between two distinct states – proliferating and depositing ECM - is necessary and sufficient to define dermal architecture. Understanding this interdependence is critical for identifying new therapeutic strategies to enhance skin regeneration.

Highlights

Tissue-scale coordination in murine dermis is driven by the interdependence of cell proliferation and ECM deposition

The tissue architecture is set by a negative feedback loop between ECM deposition/remodelling and proliferation

Fibroblast lineages lose segregation with age

Fibroblast migration is the critical discriminator between dermal development and wound healing
The segregation of vocal circuits solves a credit assignment problem associated with multi-objective reinforcement learning
Authors: Murdoch Don , Chen Ruidong , Goldberg Jesse
Published: December 2017

Motor circuits vary in topographic organization, ranging from a coarse relationship between neuron location and function to highly localized regions controlling specific behaviors. For unclear reasons, vocal learning circuits lie at this second extreme: they repeatedly evolved to be spatially segregated from other parts of the motor system. Here we show that spatially segregated motor circuits can solve a specific problem that arises when an animal tries to learn two things at once. We trained songbirds in vocal and place learning paradigms with brief strobe light flashes and noise bursts. Strobe light negatively reinforced place learning but did not affect song syllable learning. Noise bursts positively reinforced place preference but negatively reinforced syllable learning. These double dissociations indicate that vocalization-related reinforcement signals specifically target the vocal motor system, while place-related reinforcement signals specifically target the navigation system. Non-global, target-specific reinforcement signals have established utility in machine implementation of multi-objective learning. In vocal learners, such signals could enable an animal to practice vocalizing as it does other things such as forage for food or learn to walk.
Single-cell quantification of the concentration and dissociation constant of endogenous proteins
Authors: Komatsubara Akira T. , Goto Yuhei , Kondo Yohei , Matsuda Michiyuki , Aoki Kazuhiro
Published: December 2017

Kinetic simulation is a useful approach for the elucidation of complex cell-signaling systems. To perform the numerical simulations required for kinetic modeling, parameters such as the protein concentration and dissociation constant (Kd) are essential. However, only a limited number of parameters have been measured experimentally in living cells. Here, we describe a method for quantifying the concentration and Kd of endogenous proteins at the single-cell level with CRISPR/Cas9-mediated knock-in and fluorescence cross-correlation spectroscopy (FCCS). First, the mEGFP gene was knocked-in at the end of the MAPK1 gene, which encoded ERK2, through homology-directed repair or microhomology-mediated end joining. Next, the HaloTag gene was further knocked-in at the end of the RSK2 gene. Protein concentrations of endogenous ERK2-mEGFP and RSK2-HaloTag were quantified in living cells by fluorescence correlation spectroscopy (FCS), revealing substantial cellular heterogeneities. Interestingly, the levels of ERK2-mEGFP and RSK2-HaloTag were strongly positively correlated, suggesting a global mechanism underlying their expressions. In addition, FCCS measurement revealed temporal changes in the apparent Kd values of the binding between ERK2-mEGFP and RSK2-HaloTag in response to EGF stimulation. Our method provides a new approach for quantification of the endogenous protein concentration and dissociation constant in living cells.
Evolutionary expansion of DNA hypomethylation in the mammalian germline genome
Authors: Qu Jianghan , Hodges Emily , Molaro Antoine , Gagneux Pascal , Dean Matthew D. , Hannon Gregory J. , Smith Andrew D.
Published: December 2017

DNA methylation in the germline is among the most important factors influencing the evolution of mammalian genomes. Yet little is known about its evolutionary rate or the fraction of the methylome that has undergone change. We compared whole-genome, single-CpG DNA methylation profiles in sperm of seven species—human, chimpanzee, gorilla, rhesus macaque, mouse, rat, and dog—to investigate epigenomic evolution. We developed a phylo-epigenetic model for DNA methylation that accommodates the correlation of states at neighboring sites and allows for inference of ancestral states. Applying this model to the sperm methylomes, we uncovered an overall evolutionary expansion of the hypomethylated fraction of the genome, driven both by the birth of new hypomethylated regions and by extensive widening of hypomethylated intervals in ancestral species. This expansion shows strong lineage-specific aspects, most notably that hypomethylated intervals around transcription start sites have evolved to be considerably wider in primates and dog than in rodents, whereas rodents show evidence of a greater trend toward birth of new hypomethylated regions. Lineage-specific hypomethylated regions are enriched near sets of genes with common developmental functions and significant overlap across lineages. Rodent-specific and primate-specific hypomethylated regions are enriched for binding sites of similar transcription factors, suggesting that the plasticity accommodated by certain regulatory factors is conserved, despite substantial change in the specific sites of regulation. Overall our results reveal substantial global epigenomic change in mammalian sperm methylomes and point to a divergence in trans-epigenetic mechanisms that govern the organization of epigenetic states at gene promoters.
E-banking in Colombia: factors favouring its acceptance, online trust and government support
Authors: Sánchez-Torres Javier A. , Canada Francisco-Javier Arroyo , Sandoval Alexander Varon , Alzate James-Ariel Sánchez
Published: December 2017

Purpose

The purpose of this paper is to examine the adoption of e-banking in Colombia, including a comprehensive analysis of consumer trust in this type of transaction and of the impact of the current government policy to promote e-commerce.

Design/methodology/approach

An empirical investigation based on the UTAUT2 model collected data from throughout the country to develop 600 online questionnaires.

Findings

The proposed model was validated in that the factors hypothesised to build trust in the use of electronic banking were shown to be significant: trust, performance expectancy and effort expectancy had a positive impact on the use of financial websites in Colombia, while government support did not have a significant impact.

Research limitations/implications

The study explains the antecedents to trust, as well as the government support variable, and concludes by producing a model that is highly successful in predicting financial customers’ online behaviour.

Practical implications

The results can help Colombia’s Government and private banks to further develop trust and other conditions necessary for e-banking.

Social implications

Studies on the adoption of electronic banking provide users of these services solutions for their needs. Government policies to support the development of e-banking are not viewed favourably by Colombians.

Originality/value

This study is one of the first to present empirical findings on the acceptance of e-banking in Latin America; it further presents a model that integrates the most important variables needed for an analysis of the acceptance of e-banking.