bluuebunny/crossref_metadata_2025 huggingface dataset:
Using an eLearning Module to Facilitate Sepsis Knowledge Acquisition Across Multiple Institutions and Learner Disciplines
Authors: Woods Jason M. , Scott Halden F. , Mullan Paul C. , Badolato Gia , Sestokas Jeff , Sarnacki Rachel , Wolff Margaret , Lane Roni , Dawson Emily , Kaplan Ron , Zaveri Pavan
Published: August 2019

Objective

Guidelines exist for care of pediatric sepsis, but no study has assessed the benefit of electronic learning (eLearning) in this topic area. The objective of this multicenter study was to assess knowledge acquisition and retention for pediatric sepsis across multiple health care provider roles, using an adaptive and interactive eLearning module.

Methods

The study used pretest, posttest, and 90-day delayed test scores to evaluate provider knowledge after an adaptive and interactive eLearning module intervention. The eLearning module contained conditional logic-based assessments that allowed real-time adjustments of the displayed content according to each participant's demonstrated knowledge. Physicians, nurses, and advanced practice providers, primarily emergency department based, at 9 pediatric institutions were included. Changes in test scores were stratified by provider role.

Results

A total of 574 participants completed the posttest, and 296 (51.6%) of those completed the delayed test. Across all providers, there was an increase in test scores of 15.7% between the pretest and posttest (P < 0.001) with a large effect size as measured by Cramer's V. Across all providers, there was an overall test score increase of 5.2% (P < 0.001) between the pretest and delayed test, with a small effect size.

Conclusions

An eLearning module improved immediate and delayed pediatric sepsis knowledge in pediatric health care providers across multiple institutions and provider roles. Immediate knowledge gain was meaningful as indicated by effect sizes, although by the time of the delayed test, the effect was smaller. This module fills an important gap in currently available pediatric sepsis education.
Complications Associated With Electromyography
Authors: Cushman Daniel M. , Strenn Quinn , Elmer Andrew , Yang Aaron J. , Onofrei Ligia
Published: August 2019

Objectives

The aims of the study were to systematically review the available literature concerning complications due to electromyography and to review those associated with nerve conduction studies.

Design

A systematic review was undertaken of Medline and Cochrane Central Register of Controlled Trials. Any complication related to clinical electromyography written in English was included, and all bibliographies were scanned for missed articles.

Results

A total of 27 articles fit the inclusion criteria, with two observational studies, and the rest case series or case studies; 42 patients were reported. Of these, 28 patients required hospitalization and 22 required surgery or a procedure, with zero deaths reported. Needle-related complications were the most prevalent (18 patients reported), with 17 related to pneumothoraces. Disorders of hemostasis were identified in 13 patients (many were asymptomatic) and cutaneous disorders were identified in 11 patients. Only one complication was identified in the narrative review related to nerve conduction studies.

Conclusions

This systematic review identified a variety of complications related to electromyography. Although the incidence of these occurrences cannot be elucidated from the case series and case study–predominant literature, adverse events seem to be rare but can cause significant morbidity. Electromyographers should be aware of all reported complications; this review outlines all reported occurrences that fit the inclusion criteria.
Topography of the Central Retinal Artery Relevant to Retrobulbar Reperfusion in Filler Complications
Authors: Lee Shin-Hyo , Ha Tae-Jun , Lee Je-Sung , Koh Ki-Seok , Song Wu-Chul
Published: August 2019

Background:

Vision loss caused by retrograde occlusion of the central retinal artery is a serious complication of cosmetic filler injections. Salvage methods that involve applying hyaluronidases in the retrobulbar space to degrade filler materials have been proposed recently for rescuing the retinal circulation in an ophthalmic emergency.

Methods:

Sixty-six eyeballs and orbital contents were extracted from formalin-embalmed cadavers and dissected carefully to examine the topographic relationship of the central retinal artery and optic nerve. To observe the three-dimensional course of a central retinal artery that invaginates into the optic nerve, serial sections reconstructed at 100-μm intervals using software were visualized in 11 specimens.

Results:

The central retinal artery ramified from the ophthalmic artery and entered the optic nerve inferiorly at 8.7 ± 1.7 mm (mean ± SD) from the posterior margin of the eyeball. The intraneural course of a central retinal artery changed acutely between the periorbital environment of the fibrous optic nerve sheath, intermediate subarachnoid spaces, and center of the optic nerve stroma.

Conclusion:

When applying a retrobulbar approach for central retinal artery reperfusion with hyaluronidases, the reliable access route is suggested to be at a depth of 3.0 to 3.5 cm from the border of the inferolateral orbital rim, based on consideration of the entry point of the central retinal artery into the optic nerve.
Quantification of Head Shape from Three-Dimensional Photography for Presurgical and Postsurgical Evaluation of Craniosynostosis
Authors: Porras Antonio R. , Tu Liyun , Tsering Deki , Mantilla Esperanza , Oh Albert , Enquobahrie Andinet , Keating Robert , Rogers Gary F. , Linguraru Marius George
Published: August 2019

Background:

Evaluation of surgical treatment for craniosynostosis is typically based on subjective visual assessment or simple clinical metrics of cranial shape that are prone to interobserver variability. Three-dimensional photography provides cheap and noninvasive information to assess surgical outcomes, but there are no clinical tools to analyze it. The authors aim to objectively and automatically quantify head shape from three-dimensional photography.

Methods:

The authors present an automatic method to quantify intuitive metrics of local head shape from three-dimensional photography using a normative statistical head shape model built from 201 subjects. The authors use these metrics together with a machine learning classifier to distinguish between patients with (n = 266) and without (n = 201) craniosynostosis (aged 0 to 6 years). The authors also use their algorithms to quantify objectively local surgical head shape improvements on 18 patients with presurgical and postsurgical three-dimensional photographs.

Results:

The authors’ methods detected craniosynostosis automatically with 94.74 percent sensitivity and 96.02 percent specificity. Within the data set of patients with craniosynostosis, the authors identified correctly the fused sutures with 99.51 percent sensitivity and 99.13 percent specificity. When the authors compared quantitatively the presurgical and postsurgical head shapes of patients with craniosynostosis, they obtained a significant reduction of head shape abnormalities (p < 0.05), in agreement with the treatment approach and the clinical observations.

Conclusions:

Quantitative head shape analysis and three-dimensional photography provide an accurate and objective tool to screen for head shape abnormalities at low cost and avoiding imaging with radiation and/or sedation. The authors’ automatic quantitative framework allows for the evaluation of surgical outcomes and has the potential to detect relapses.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, I.
Involvement of PDGF-BB and IGF-1 in Activation of Human Schwann Cells by Platelet-Rich Plasma
Authors: Sowa Yoshihiro , Kishida Tsunao , Tomita Koichi , Adachi Tetsuya , Numajiri Toshiaki , Mazda Osam
Published: August 2019

Background:

Platelet-rich plasma contains high concentrations of growth factors that stimulate proliferation and migration of various cell types. Earlier experiments demonstrated that local platelet-rich plasma administration activates Schwann cells to improve axonal regeneration at a transected peripheral nerve lesion. However, the optimal concentration of human platelet-rich plasma for activation of human Schwann cells has not been determined, and mechanisms by which platelet-rich plasma activates Schwann cells remain to be clarified.

Methods:

Human Schwann cells were cultured with various concentrations of platelet-rich plasma in 5% fetal bovine serum/Dulbecco’s Modified Eagle Medium. Cell viability, microchemotaxis, flow cytometry, and quantitative real-time polymerase chain reaction assays were performed to assess proliferation, migration, cell cycle, and neurotrophic factor expression of the human Schwann cells, respectively. Human Schwann cells were co-cultured with neuronal cells to assess their capacity to induce neurite extension. Neutralizing antibodies for platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) were added to the culture to estimate contribution of these cytokines to human Schwann cell stimulation by platelet-rich plasma.

Results:

An addition of platelet-rich plasma at 5% strongly elevated proliferation, migration, and neurotrophic factor production of human Schwann cells. Both PDGF-BB and IGF-1 may be involved in mitogenic effect of platelet-rich plasma on human Schwann cells, and PDGF-BB may also play an important role in the migration-inducing effect of platelet-rich plasma. Neutralization of both PDGF-BB and IGF-1 cancelled the promoting effect of platelet-rich plasma on neurite-inducing activity of human Schwann cells.

Conclusion:

This study may suggest the optimal concentration of platelet-rich plasma for human Schwann cell stimulation and potential mechanisms underlying the activation of human Schwann cells by platelet-rich plasma, which may be quite useful for platelet-rich plasma therapy for peripheral nerve regeneration.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Mechanical Signals Induce Dedifferentiation of Mature Adipocytes and Increase the Retention Rate of Fat Grafts
Authors: Ma Jingjing , Xia, M.D. Jing , Gao Jianhua , Lu Feng , Liao Yunjun
Published: August 2019

Background:

Mature adipocytes dedifferentiate in vivo on application of a soft-tissue expander. Dedifferentiated adipocytes can proliferate and redifferentiate. This study used tissue expanders to pretreat adipose flaps, to increase the retention rate after fat graft.

Methods:

A soft-tissue expander and silicone sheet were implanted beneath the left and right inguinal fat pads of rats, respectively. After 7 days of expansion, the adipose tissue derived from the pads was transplanted beneath dorsal skin. Samples were harvested at various time points, and histologic, immunohistochemical, and gene expression analyses were conducted. Mature adipocytes were cultured in vitro under a pressure of 520 Pa. Changes in cell morphology, the cytoskeleton, and expression of mechanical signal–related proteins were investigated.

Results:

Pressure in adipose flaps increased to 25 kPa on expansion. Mature adipocytes dedifferentiated following expansion. At 1 week after transplantation, the expression of vascular endothelial growth factor (p < 0.05) was higher in the expanded group. The retention rate at 12 weeks after transplantation was higher in the expanded group (56 ± 3 percent) than in the control group (32 ± 3 percent) (p < 0.05), and the surviving/regenerating zones (p < 0.01) were wider. The lipid content of mature adipocytes gradually decreased on culture under increased pressure, and these cells regained a proliferative capacity. This was accompanied by increased expression of mechanical signal--related proteins (p < 0.05).

Conclusions:

Mechanical signals may induce dedifferentiation of mature adipocytes. Dedifferentiated adipocytes increase the retention rate of fat grafts by acting as seed cells.
Outcomes, Challenges, and Pitfalls after Targeted Muscle Reinnervation in High-Level Amputees: Is It Worth the Effort?
Authors: Salminger Stefan , Sturma Agnes , Roche Aidan D. , Mayer Johannes A. , Gstoettner Clemens , Aszmann Oskar C.
Published: August 2019

Background:

Although the distal targets have been lost in proximal upper limb amputees, the neural signals for intuitive hand and arm function are still available and thus can be incorporated into more useful prosthetic function using targeted muscle reinnervation technique. In this article, the authors present their outcomes and range of indications in addition to experiences and pitfalls after 30 targeted muscle reinnervation cases at above-elbow and shoulder disarticulation level of amputation.

Methods:

Thirty patients with above-elbow or shoulder disarticulation amputations were enrolled between 2012 and 2017. Indications for targeted muscle reinnervation surgery differed between improvement of prosthetic function (n = 19) and/or pain (n = 11). Functional outcome was evaluated with the Action Research Arm Test, the Southampton Hand Assessment Procedure, and the Clothespin-Relocation Test. Functional evaluation was performed at least at 6 months after final prosthetic fitting.

Results:

All nerve transfers were successful and provided independent myoelectric signals. The 10 patients available for final functional evaluation showed Action Research Arm Test scores of 20.4 ± 1.9 and Southampton Hand Assessment Procedure scores of 40.5 ± 8.1. The Clothespin-Relocation Test showed a mean time of 34.3 ± 14.4 seconds.

Conclusions:

Targeted muscle reinnervation has improved prosthetic control and revolutionized neuroma treatment in upper limb amputees. Still, the rate of abandonment even after targeted muscle reinnervation surgery has been shown high, and several advances within the biotechnological interface will be needed to improve prosthetic function and acceptance in these patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Magnetic Resonance Imaging for the Follow-up of Treated Thymic Epithelial Malignancies
Authors: Kerpel Ariel , Beytelman Arkadi , Ofek Efrat , Marom Edith M.
Published: August 2019

Purpose:

The purpose of this article was to compare magnetic resonance imaging (MRI) depiction of thymic malignancy progression/recurrence with that of computed tomography (CT).

Methods:

We retrospectively reviewed all surgically treated thymic epithelial malignancy (TEM) patients between 2011 and 2018 who were followed-up with chest CT and MRI. We compared the detection of recurrence and metastatic disease between the CT and MRI scans in each of these patients.

Results:

Of 187 patients treated in our institution for TEM, 22 were followed-up with both CT and MRI. TNM stage at diagnosis was as follows: I (n=14), II (n=1), IIIa (n=4), IIIb (n=2), IVa (n=1), and IVb (n=0). Patients were followed-up for a mean of 6.2 years, range 0.7 to 17.7 years. The mean interval between CT and MRI was 5.4 (range, 1 to 15) months. Most patients had no recurrence (n=16), 4 had recurrence after R0 or R1 resection, 1 had stable disease, and 1 had progression of disease after R2 resection. CT and MRI performed equally in the identification of pleural spread (n=5), lymphadenopathy (n=4), and pulmonary metastases (n=1). Retrosternal recurrence (n=1) was identified by MRI despite sternotomy wire artifacts. MRI identified bone involvement and extension of disease into the thecal sac earlier and more readily. Three patients had an indeterminate mediastinal finding on CT that was correctly identified as a benign cyst or pericardial fluid collection by MRI.

Conclusion:

MRI is an alternative option to follow-up patients after treatment for TEM. However, for those with metallic sternotomy wires, we recommend alternating the follow-up with CT as well.
An Analysis of Aesthetic Refinements in 120 Secondary Cleft Rhinoplasties
Authors: Kehrer Andreas , Nijhuis Tim H. J. , Lonic Daniel , Heidekrueger Paul I. , Kehrer Michael , Taeger Christian D. , Willemsen Sten , Prantl Lukas , van der Meulen Jacques J. J. N. M.
Published: August 2019

Background

Secondary cleft nose rhinoplasty remains a challenging procedure. Cartilage memory and scar contraction are problematic factors. The need for more detailed procedures for secondary reconstruction in this patient population has arisen. Contemporary refinements demonstrate a highly structured approach. We conducted a retrospective study evaluating the aesthetic results of cleft patients who underwent secondary rhinoplasty.

Methods

In a retrospective study, a photometric analysis of cleft patients operated in the period 2003–2011 was conducted. Reconstructive methods were documented. Pre- and postoperative photographs of cleft rhinoplasty patients were evaluated using a standardized protocol. Nostril width ratio, columellar angle, tip projection ratio, and nasolabial angle served as objective instruments. The Unilateral Cleft Lip Surgical Outcomes Evaluation score was chosen for external photometric rating and rated blindly by 2 external individual plastic surgeons as independent nonbiased reviewers. The interrater and intrarater reliabilities were calculated using the Cohen kappa coefficient (κ).

Results

A total of 120 secondary rhinoplasties in 85 uni- and bilateral cleft patients could be included. Mean follow-up was 20 months. A total of 60 (71%) patients needed additional bone grafting (chin/pelvis), and 23 (27%) patients a LeFort I osteotomy. In one third of the secondary rhinoplasties, a medial and/or lateral osteotomy was performed (34%). In one fourth (24%), an external septoplasty was considered necessary. In 55% (47 patients) of the cases, a columellar strut was used. Excluding bone grafts, a total of 173 other grafts (mean of 2 grafts/patient) were applied. Postoperative measurements for nostril width ratio and columellar angle were statistically significant. A structured approach with contemporary refinements is described in detail. Intra- and interrater reliabilities for photometric assessment according to the Unilateral Cleft Lip Surgical Outcomes Evaluation score are shown.

Conclusions

A structured approach for secondary cleft rhinoplasty yields satisfying, reproducible, and stable results.
Magnetic Resonance Imaging Features of Collet-Sicard Syndrome Associated With Glomus Jugulare Paraganglioma
Authors: Mutlu Vahit , Ogul Hayri
Published: August 2019

Collet-Sicard syndrome is an unusual disorder. The authors here demonstrated the Magnetic resonance (MR) imaging findings of the Collet-Sicard syndrome associated with glomus jugulare tumor. Neoplastic or non-neoplastic lesion of skull base can cause Collet-Sicard syndrome. MR imaging can be used successfully to demonstrate the etiology of this syndrome.
Endothelial cell dysfunction during anoxia-reoxygenation is associated with a decrease in adenosine triphosphate levels, rearrangement in lipid bilayer phosphatidylserine asymmetry, and an increase in endothelial cell permeability
Authors: Sadjadi Javid , Strumwasser Aaron M. , Victorino Gregory P.
Published: August 2019

BACKGROUND

Phosphatidylserine (PS) is normally confined in an energy-dependent manner to the inner leaflet of the lipid cell membrane. During cellular stress, PS is exteriorized to the outer layer, initiating a cascade of events. Because cellular stress is often accompanied by decreased energy levels and because maintaining PS asymmetry is an energy-dependent process, it would make sense that cellular stress associated with decreased energy levels is also associated with PS exteriorization that ultimately leads to endothelial cell dysfunction. Our hypothesis was that anoxia-reoxygenation (A-R) is associated with decreased adenosine triphosphate (ATP) levels, increased PS exteriorization on endothelial cell membranes, and increased endothelial cell membrane permeability.

METHODS

The effect on ATP levels during A-R was measured via colorimetric assay in cultured cells. To measure the effect of A-R on PS levels, cultured cells underwent A-R and exteriorized PS levels and also total cell PS were measured via biofluorescence assay. Finally, we measured endothelial cell monolayer permeability to albumin after A-R.

RESULTS

The ATP levels in cell culture decreased 27% from baseline after A-R (p< 0.02). There was over a twofold increase in exteriorized PS as compared with controls (p< 0.01). Interestingly, we found that during A-R, the total amount of cellular PS increased (p< 0.01). The finding that total PS changed twofold over normal cells suggested that not only is there a change in the distribution of PS across the cell membrane, but there may also be an increase in the amount of PS inside the cell. Finally, A-R increased endothelial cell monolayer permeability (p< 0.01).

CONCLUSION

We found that endothelial cell dysfunction during A-R is associated with decreased ATP levels, increased PS exteriorization, and increased in monolayer permeability. This supports the idea that PS exteriorization may a key event during clinical scenarios involving oxygen lack and may 1 day lead to novel therapies in these situations.
Highly variable COI haplotype diversity between three species of invasive pest fruit fly reflects remarkably incongruent demographic histories
Authors: Doorenweerd Camiel , Jose Michael San , Barr Norman , Leblanc Luc , Rubinoff Daniel
Published: August 2019

Distance decay principles predict that species with larger geographic ranges would have greater intraspecific genetic diversity than more restricted species. However, invasive pest species may not follow this prediction, with confounding implications for tracking phenomena including original ranges, invasion pathways and source populations. We sequenced an 815 base-pair section of the COI gene for 441 specimens ofBactrocera correcta, 214B. zonataand 372Zeugodacus cucurbitae; three invasive pest fruit fly species with overlapping hostplants. For each species, we explored how many individuals would need to be included in a study to sample the majority of their haplotype diversity. We also tested for phylogeographic signal and used demographic estimators as a proxy for invasion potency. We find contrasting patterns of haplotype diversity amongst the species, whereB. zonatahas the highest diversity but most haplotypes were represented by singletons;B. correctahas ∼7 dominant haplotypes more evenly distributed;Z. cucurbitaehas a single dominant haplotype with closely related singletons in a ‘star-shape’ surrounding it. We discuss how these differing patterns relate to their invasion histories. None of the species showed meaningful phylogeographic patterns, possibly due to gene-flow between areas across their distributions, obscuring or eliminating substructuring.
Kin and group selection are both flawed but useful data analysis tools
Authors: smith jeff , Inglis R. Fredrik
Published: August 2019

For understanding the evolution of social behavior in microbes, mathematical theory can aid empirical research but is often only used as a qualitative heuristic. How to properly formulate social evolution theory has also been contentious. Here we evaluate kin and multilevel selection theory as tools for analyzing microbial data. We reanalyze published datasets that share a common experimental design and evaluate these theories in terms of data visualization, statistical performance, biological interpretation, and quantitative comparison across systems. We find that the canonical formulations of both kin and multilevel selection are almost always poor analytical tools because they use statistical regressions that are poorly specified for the strong selection and nonadditive fitness effects common in microbial systems. Analyzing both individual and group fitness outcomes helps clarify the biology of selection. We also identify analytical practices in empirical research that suggest how theory might better handle the challenges of microbial data. A quantitative, data-driven approach thus shows how kin and multilevel selection theory both have substantial room for improvement as tools for understanding social evolution in all branches of life.
Predicting changes in bee assemblages following state transitions at North American dryland ecotones
Authors: Kazenel Melanie R. , Wright Karen W. , Bettinelli Julieta , Griswold Terry L. , Whitney Kenneth D. , Rudgers Jennifer A.
Published: August 2019

Drylands worldwide are experiencing ecosystem state transitions: the expansion of some ecosystem types at the expense of others. Bees in drylands are particularly abundant and diverse, with potential for large compositional differences and seasonal turnover across ecotones. To better understand how future ecosystem state transitions may influence bees, we compared bee assemblages and their seasonality among sites at the Sevilleta National Wildlife Refuge (NM, USA) that represent three dryland ecosystem types (and two ecotones) of the southwestern U.S. (Plains grassland, Chihuahuan Desert grassland, and Chihuahuan Desert shrubland). Using passive traps, we caught bees during two-week intervals from March – October, 2002 – 2014. The resulting dataset included 302 bee species and 56 genera. Bee abundance, composition, and diversity differed among ecosystems, indicating that future state transitions could alter bee assemblage composition in our system. We found strong seasonal bee species turnover, suggesting that bee phenological shifts may accompany state transitions. Common species drove the observed trends, and both specialist and generalist bee species were indicators of ecosystem types or months; these species could be sentinels of community-wide responses to future shifts. Our work suggests that predicting the consequences of global change for bee assemblages requires accounting for both within-year and among-ecosystem variation.
Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection
Authors: Beckwith Kai S. , Beckwith Marianne S. , Ullmann Sindre , Sætra Ragnhild , Kim Haelin , Marstad Anne , Åsberg Signe E. , Strand Trine A. , Stenmark Harald A. , Flo Trude H.
Published: August 2019

Mycobacterium tuberculosis (Mtb) is a major global health problem and causes extensive cytotoxicity in patient cells and tissues. Here we define an NLRP3, caspase-1 and gasdermin D-mediated pathway to pyroptosis in human monocytes following exposure to Mtb. We demonstrate an ESX-1 mediated, contact-induced plasma membrane (PM) damage response that occurs during phagocytosis or from the cytosolic side of the PM after phagosomal rupture in Mtb infected cells. This PM injury in turn causes K+ efflux and activation of NLRP3 dependent IL-1β release and pyroptosis, facilitating the spread of Mtb to neighbouring cells. Further we reveal a dynamic interplay of pyroptosis with ESCRT-mediated PM repair. Collectively, these findings reveal a novel mechanism for pyroptosis and spread of infection acting through dual PM disturbances both during and after phagocytosis. We also highlight dual PM damage as a common mechanism utilized by other NLRP3 activators that have previously been shown to act through lysosomal damage.

Graphical abstract
Independent evolution towards large body size in the distinctive Faroe Island mice
Authors: Wilches Ricardo , Beluch William H. , McConnell Ellen , Tautz Diethard , Chan Yingguang Frank
Published: August 2019

Most traits in nature involve the collective action of many genes. Traits that evolve repeatedly are particularly revealing about how selection may act on traits. In mice, large body size has evolved repeatedly on islands and under artificial selection in the laboratory. Identifying the loci and genes involved in this process may shed light on the evolution of complex, polygenic traits. Here, we have mapped the genetic basis of body size variation by making a genetic cross between mice from the Faroe Islands, which are among the largest and most distinctive populations of mice in the world, and a laboratory mouse strain selected for small body size, SM/J. Using this F2 intercross of 841 animals, we have identified 102 loci controlling various aspects of body size, weight and growth hormone levels. By comparing against other studies, including the use of a joint meta-analysis, we found that the loci involved in the evolution of large size in the Faroese mice were largely independent from those of a different island population or other laboratory strains. We conclude that colonization bottleneck, historical hybridization, or the redundancy between multiple loci have resulted in the Faroese mice achieving an outwardly similar phenotype through a distinct evolutionary path.
Comparative pathway enrichment analysis in gastrointestinal cell lines Caco-2, HT-29, HEPG2, and colon fibroblasts using a custom expression panel for tight-junction and cytoskeletal regulatory genes
Authors: Robinson JM
Published: August 2019

This brief report details results from a comparative analysis of Nanostring expression data between cell lines HEPG2, Caco-2, HT-29, and colon fibroblasts. Raw and normalized data are available publicly in the NCBI GEO/Bioproject databases. Results identify cell-line specific variations in gene expression relevant to intestinal epithelial function.
Genome sequencing and neurotoxin diversity of a wandering spider Pardosa pseudoannulata (pond wolf spider)
Authors: Yu Na , Li Jingjing , Liu Meng , Huang Lixin , Bao Haibo , Yang Zhiming , Zhang Yixi , Gao Haoli , Wang Zhaoying , Yang Yuanxue , Van Leeuwen Thomas , Millar Neil S. , Liu Zewen
Published: August 2019

Spiders constitute an extensive and diverse branch of the phylum Arthropoda. Whereas the genomes of four web-weaver spider species and a single cave-living spider have been determined, similar studies have not been reported previously for a wandering spider. The pond wolf spider, Pardosa pseudoannulata, is a wandering hunter that immobilizes prey using venom rather than a web. It is also an important predator against a range of agriculturally important insect pests. The increasing interest in its wandering lifestyle and in the potential of spider venom as a tool for pest control have prompted a detailed study on this wandering spider species. We have generated a high-quality genome sequence of P. pseudoannulata and analysed genes associated with the production of silk and venom toxins. Sequencing reveals that P. pseudoannulata has a large genome of 4.26 Gb. The presence of only 16 spidroin genes and four types of silk glands is consistent with the moderate use of silk and the lack of a prey-catching web. A large number of genes encode neurotoxins and there is evidence that the majority are highly selective for invertebrates. Comparison between spider species reveals a correlation between spider neurotoxin selectivity for target organisms and spider prosoma size, suggesting a possible coevolution of these two features. The genome data provides valuable insights into the biology of P. pseudoannulata and its potential role as a natural enemy in pest control.
Spooky interaction at a distance in cave and surface dwelling electric fishes
Authors: Fortune Eric S. , Andanar Nicole , Madhav Manu , Jayakumar Ravi , Cowan Noah J. , Bichuette Maria Elina , Soares Daphne
Published: August 2019

Glass knifefish (Eigenmannia) are a group of weakly electric fishes found throughout the Amazon basin. We made recordings of the electric fields of two populations of freely behavingEigenmanniain their natural habitats: a troglobitic population of blind cavefish (Eigenmannia vicentespelaea) and a nearby epigean (surface) population (Eigenmannia trilineata). These recordings were made using a grid of electrodes to determine the movements of individual fish in relation to their electrosensory behaviors. The strengths of electric discharges in cavefish were larger than in surface fish, which may be a correlate of increased reliance on electrosensory perception and larger size. Both movement and social signals were found to affect the electrosensory signaling of individualEigenmannia. Surface fish were recorded while feeding at night and did not show evidence of territoriality. In contrast, cavefish appeared to maintain territories. Surprisingly, we routinely found both surface and cavefish with sustained differences in electric field frequencies that were below 10 Hz despite being within close proximity of less than one meter. A half century of analysis of electrosocial interactions in laboratory tanks suggest that these small differences in electric field frequencies should have triggered the jamming avoidance response. Fish also showed significant interactions between their electric field frequencies and relative movements at large distances, over 1.5 meters, and at high differences in frequencies, often greater than 50 Hz. These interactions are likely envelope responses in which fish alter their EOD frequency in relation to changes in the depth of modulation of electrosocial signals.
Single cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination
Authors: Mayère Chloé , Neirijnck Yasmine , Sararols Pauline , Rands Chris M , Stévant Isabelle , Kühne Françoise , Chassot Anne-Amandine , Chaboissier Marie-Christine , Dermitzakis Emmanouil T. , Nef Serge
Published: August 2019

Despite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the Bone morphogenic protein (BMP) and Nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data is available on a web platform and provides a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function and disease.
Capsule Networks as Recurrent Models ofGrouping and Segmentation
Authors: Doerig Adrien , Schmittwilken Lynn , Sayim Bilge , Manassi Mauro , Herzog Michael H.
Published: August 2019

Classically, visual processing is described as a cascade of local feedforward computations. Feedforward Convolutional Neural Networks (ffCNNs) have shown how powerful such models can be. However, using visual crowding as a well-controlled challenge, we previously showed that no classic model of vision, including ffCNNs, can explain human global shape processing (1). Here, we show that Capsule Neural Networks (CapsNets; 2), combining ffCNNs with recurrent grouping and segmentation, solve this challenge. We also show that ffCNNs and standard recurrent CNNs do not, suggesting that the grouping and segmentation capabilities of CapsNets are crucial. Furthermore, we provide psychophysical evidence that grouping and segmentation are implemented recurrently in humans, and show that CapsNets reproduce these results well. We discuss why recurrence seems needed to implement grouping and segmentation efficiently. Together, we provide mutually reinforcing psychophysical and computational evidence that a recurrent grouping and segmentation process is essential to understand the visual system and create better models that harness global shape computations.

Author Summary

Feedforward Convolutional Neural Networks (ffCNNs) have revolutionized computer vision and are deeply transforming neuroscience. However, ffCNNs only roughly mimic human vision. There is a rapidly expanding body of literature investigating differences between humans and ffCNNs. Several findings suggest that, unlike humans, ffCNNs rely mostly on local visual features. Furthermore, ffCNNs lack recurrent connections, which abound in the brain. Here, we use visual crowding, a well-known psychophysical phenomenon, to investigate recurrent computations in global shape processing. Previously, we showed that no model based on the classic feedforward framework of vision can explain global effects in crowding. Here, we show that Capsule Neural Networks (CapsNets), combining ffCNNs with recurrent grouping and segmentation, solve this challenge. ffCNNs and recurrent CNNs with lateral and top-down recurrent connections do not, suggesting that grouping and segmentation are crucial for human-like global computations. Based on these results, we hypothesize that one computational function of recurrence is to efficiently implement grouping and segmentation. We provide psychophysical evidence that, indeed, grouping and segmentation is based on time consuming recurrent processes in the human brain. CapsNets reproduce these results too. Together, we provide mutually reinforcing computational and psychophysical evidence that a recurrent grouping and segmentation process is essential to understand the visual system and create better models that harness global shape computations.
Autophagy mediates temporary reprogramming and dedifferentiation in plant somatic cells
Authors: Rodriguez Eleazar , Chevalier Jonathan , Olsen Jakob , Ansbøl Jeppe , Kapousidou Vaitsa , Zuo Zhangli , Svenning Steingrim , Loefke Christian , Koemeda Stefanie , Drozdowskyj Pedro Serrano , Jez Jakub , Durnberger Gerhard , Kuenzl Fabian , Schutzbier Michael , Mechtler Karl , Lolle Signe , Dagdas Yasin , Petersen Morten
Published: August 2019

Somatic cells acclimate to changes in the environment by temporary reprogramming. Much has been learned about transcription factors that induce these cell-state switches in both plants and animals, but how cells rapidly modulate their proteome remains elusive. Here, we show rapid induction of autophagy during temporary reprogramming in plants triggered by phytohormones, immune and danger signals. Quantitative proteomics following sequential reprogramming revealed that autophagy is required for timely decay of previous cellular states and for tweaking the proteome to acclimate to the new conditions. Signatures of previous cellular programs thus persist in autophagy deficient cells, affecting cellular decision-making. Concordantly, autophagy deficient cells fail to acclimatize to dynamic climate changes. Similarly, they have defects in dedifferentiating into pluripotent stem cells, and redifferentiation during organogenesis. These observations indicate that autophagy mediates cell state switches that underlie somatic cell reprogramming in plants and possibly other organisms, and thereby promotes phenotypic plasticity.
Sex chromosomes control vertical transmission of feminizing Wolbachia symbionts in an isopod
Authors: Becking Thomas , Chebbi Mohamed Amine , Giraud Isabelle , Moumen Bouziane , Laverré Tiffany , Caubet Yves , Peccoud Jean , Gilbert Clément , Cordaux Richard
Published: August 2019

Microbial endosymbiosis is widespread in animals, with major ecological and evolutionary implications. Successful symbiosis relies on efficient vertical transmission through host generations. However, when symbionts negatively affect host fitness, hosts are expected to evolve suppression of symbiont effects or transmission. Here we show that sex chromosomes control vertical transmission of feminizing Wolbachia endosymbionts in the isopod Armadillidium nasatum. Theory predicts that the invasion of an XY/XX species by cytoplasmic sex ratio distorters is unlikely because it leads to fixation of the unusual (and often lethal or infertile) YY genotype. We demonstrate that A. nasatum X and Y sex chromosomes are genetically highly similar and YY individuals are viable and fertile, thereby enabling Wolbachia spread in this XY-XX species. Nevertheless, we show that Wolbachia cannot drive fixation of YY individuals because infected YY females do not transmit Wolbachia to their offspring, unlike XX and XY females. The genetic basis fits the model of a Y-linked recessive allele (associated with an X-linked dominant allele), in which the homozygous state suppresses Wolbachia transmission. Moreover, production of all-male progenies by infected YY females restores a balanced sex ratio at the host population level. This suggests that blocking of Wolbachia transmission by YY females may have evolved to suppress feminization, thereby offering a whole new perspective on the evolutionary interplay between microbial symbionts and host sex chromosomes.
The genome of a subterrestrial nematode reveals an evolutionary strategy for adaptation to heat
Authors: Weinstein Deborah J. , Allen Sarah E. , Lau Maggie C. Y. , Erasmus Mariana , Asalone Kathryn C. , Walters-Conte Kathryn , Deikus Gintaras , Sebra Robert , Borgonie Gaetan , van Heerden Esta , Onstott Tullis C. , Bracht John R.
Published: August 2019

The nematodeHalicephalobus mephistowas originally discovered inhabiting a deep terrestrial aquifer 1.3 km underground.H. mephistocan thrive under conditions of abiotic stress including heat and minimal oxygen, where it feeds on a community of both chemolithotrophic and heterotrophic prokaryotes in an unusual ecosystem isolated from the surface biosphere. Here we report the comprehensive genome and transcriptome of this organism, identifying a signature of adaptation: an expanded repertoire of 70 kilodalton heat-shock proteins (Hsp70) and avrRpt2 induced gene 1 (AIG1) proteins. We find that positive selection has driven the expansion of Hsp70 genes, which are also transcriptionally induced upon growth under heat stress. We further show that AIG1 may have been acquired by horizontal gene transfer (HGT) from a rhizobial fungus. Over one-third of the genes ofH. mephistoare novel, highlighting the divergence of this nematode from other sequenced organisms. This work sheds light on the genomic strategies of adaptation to heat in the first complete subterrestrial eukaryotic genome.
Suppression of membranous LRP5 recycling, WNT/β-catenin signaling, and colorectal tumorigenesis by 15-LOX-1 peroxidation of PI3P_linoleic acid
Authors: Liu Fuyao , Zuo Xiangsheng , Liu Yi , Deguchi Yasunori , Moussalli Micheline J. , Chen Weidong , Yang Peiying , Wei Bo , Tan Lin , Lorenzi Philip L. , Gao Shen , Jaoude Jonathan C. , Mehdizadeh Amir , Ann Valentin Lovie , Wei Daoyan , Shureiqi Imad
Published: August 2019

Aberrant Wnt/β-catenin activation is a major driver of colorectal cancer (CRC), which is typically initiated byAPCmutations. Additional modifiable factors beyondAPCmutations have been recognized to be important for further potentiation of aberrant β-catenin activation to promote colorectal tumorigenesis. These factors have yet to be clearly identified. Western-type diets are increasingly enriched in linoleic acid (LA). LA-enriched diet however promotes chemically-induced colorectal tumorigenesis in rodent models. Furthermore, the main metabolizing enzyme of LA, 15-lipoxygenase-1 (15-LOX-1), is transcriptionally silenced in CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling to modulate colorectal tumorigenesis is poorly understood. Herein, we report that high dietary LA promoted colorectal tumorigenesis in mice with intestinally targetedAPCmutation (ApcΔ580) by upregulating a Wnt receptor, LRP5 expression, and β-catenin activation. 15-LOX-1 transgenic expression in intestinal epithelial cells suppressed LRP5 expression, β-catenin activation and subsequently CRC in these mice. In particular, 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) into PI3P_13-HODE decreased PI3P binding to SNX17and LRP5, which inhibited LRP5 recycling from endosomes to the plasma membrane, thereby leading to an increase of LRP5 lysosomal degradation. Our findings demonstrate for the first time that 15-LOX-1 metabolism of LA in PI3P to regulate LRP5 membrane abundance is a modifiable factor of Wnt/β-catenin aberrant signaling that could be potentially therapeutically targeted to suppress colorectal tumorigenesis and progression.
Genome sequencing for early-onset dementia: high diagnostic yield and frequent observation of multiple contributory alleles
Authors: Cochran J. Nicholas , McKinley Emily C. , Cochran Meagan , Amaral Michelle D. , Moyers Bryan A. , Lasseigne Brittany N. , Gray David E. , Lawlor James M.J. , Prokop Jeremy W. , Geier Ethan G. , Holt James M. , Thompson Michelle L. , Newberry J. Scott , Yokoyama Jennifer S. , Worthey Elizabeth A. , Geldmacher David S. , Love Marissa Natelson , Cooper Gregory M. , Myers Richard M. , Roberson Erik D.
Published: August 2019

We assessed the utility of genome sequencing for early-onset dementia. Participants were selected from a memory disorders clinic. Genome sequencing was performed along withC9orf72repeat expansion testing. All returned sequencing results were Sanger validated clinically. Prior clinical diagnoses included Alzheimer’s disease, frontotemporal dementia, and unspecified dementia. The mean age-of-onset was 54 (41–76). 50% of patients had a strong family history, 37.5% had some, and 12.5% had no known family history. Nine of 32 patients (28%) had a variant defined as pathogenic or likely pathogenic (P/LP) by American College of Medical Genetics standards, including variants inAPP,C9orf72,CSF1R, andMAPT. Nine patients (including three with P/LP variants) harbored established risk alleles with moderate penetrance (odds ratios of about 2–5) inABCA7,AKAP9,GBA,PLD3,SORL1, andTREM2. All six patients harboring these moderate penetrance variants but not P/LP variants also had one or twoAPOEε4 alleles. One patient had twoAPOEε4 alleles with no other established contributors. In total, 16 patients (50%) harbored one or more genetic variants likely to explain symptoms. We identified variants of uncertain significance (VUSs) inABI3, ADAM10, ARSA, GRID2IP, MME, NOTCH3, PLCD1, PSEN1, TM2D3, TNK1, TTC3, and VPS13C, also often along with other variants. In summary, genome sequencing for early-onset dementia demonstrated high utility, with particular advantages where targeted testing may fail such as atypical variant-disease associations or presence of multiple moderate impact alleles. One or more established contributory alleles is often present in early-onset dementia, supporting an oligogenic model.