bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Auricular Subunit Models for Cartilage Framework Fabrication: Our Preliminary Experience
Authors: Wang Qianwen , Wang Yue , Zhou Xu , Zhang Qingguo
Published: September 2021

Background:

Three-dimensional (3D) digital imaging and printing techniques have been popularly applied in microtia reconstruction. However, there is a lack of clinical report of using them to create 3D printed ear subunit models for cartilage framework fabrication.

Methods:

A retrospective study of patients who underwent auricle reconstruction with 3D templates was performed. Patients’ demography, surgical complications, framework accuracy, and aesthetic outcomes of the reconstructed auricles were analyzed.

Results:

Twenty cases included in this study. Complications were minor. The average (median) assessing scores for the framework quality and the reconstructed auricle aesthetics were 8.50 (8) and 8.30 (8), respectively.

Conclusions:

Our study found that the use of custom-printed tridimensional ear subunit models achieved a relatively high framework precision and gained good outcomes of the reconstructed ears.

Level of Evidence: Level IV.
Clinical Applications of Augmented Reality Technology in Microsurgical Planning of Head and Neck Reconstruction
Authors: Kwon Jin Geun , Hong Dae Won , Choi Jong Woo
Published: September 2021

Background:

To perform head and neck reconstruction, the exact location of recipient vessels must be evaluated preoperatively. This study aimed to superimpose arterial and venous pathways identified by computed tomography angiography (CTA) on patients using augmented reality (AR) techniques to freely select recipient vessels.

Methods:

Patients who underwent reconstructive microsurgery due to defects on the scalp, forehead, and glabella from July 2019 to October 2019 were enrolled. The superficial temporal artery (STA) and superficial temporal vein (STV) were marked using hand-held Doppler. Furthermore, the three-dimensional reconstructed CTA image was superimposed on the patient's face using a smartphone application, Camera-Lucida, and marked. The accuracy of mapping was evaluated intraoperatively. Success rates and the time consumed for mapping were compared.

Results:

Twelve patients underwent preoperative marking. Success rates of STA mapping using the AR technology and hand-held Doppler were 100% and 83%, respectively (P = 0.48). The mean time consumed for STA marking was 90.2 ± 17.7 seconds and 121.0 ± 117.7 seconds, respectively (P 
= 0.75). The success rate of STY marking with the AR technology was superior to that with hand-held Doppler (100% versus 58.3%; P = 0.037). STY marking was faster with the AR technology than with hand-held Doppler (mean time, 91.2 ± 25.7 seconds versus 94.5 ± 101.6 seconds; P = 0.007).

Conclusions:

The AR technology could be the paradigm shift in the field of microsurgical reconstruction. it can connect threedimensional CTA data with patient topography, leading to not only more precise operations but also improved outcomes in patients undergoing microsurgical reconstruction.
The patient’s voice matters: The impact of advance directives on elderly trauma patients
Authors: Lee Janet S. , Khan Abid D. , Dorlac Warren C. , Dunn Julie , McIntyre Robert C. , Wright Franklin L. , Platnick K. Barry , Brockman Valerie , Vega Stephanie A. , Cofran Jessica M. , Duero Colleen , Schroeppel Thomas J.
Published: September 2021

BACKGROUND

Geriatric trauma rates are increasing, yet trauma centers often struggle to provide autonomy regarding decision making to these patients. Advance care planning can assist with this process. Currently, there are limited data on the impact of advance directives (ADs) in elderly trauma patients. The purpose of this study was to evaluate the prevalence of preinjury AD in geriatric trauma patients and its impact on outcomes, with the hypothesis that ADs would not be associated with an increase in mortality.

METHODS

A multicenter retrospective review was conducted on patients older than 65 years with traumatic injury between 2017 and 2019. Three Level I trauma centers and one Level II trauma center were included. Exclusion criteria were readmission, burn injury, transfer to another facility, discharge from emergency department, and mortality prior to being admitted.

RESULTS

There were 6,135 patients identified; 751 (12.2%) had a preinjury AD. Patients in the AD+ group were older (86 vs. 77 years, p < 0.0001), more likely to be women (67.0% vs. 54.8%, p < 0.0001), and had more comorbidities. Hospital length of stay and ventilator days were similar. In-hospital mortality occurred in 236 patients, and 75.4% of them underwent withdrawal of care (WOC). The mortality rate was higher in AD+ group (10.5% vs. 2.9%, p < 0.0001). No difference was seen in the rate of AD between the WOC+ and WOC– group (31.5% vs. 39.6%, p = 0.251). A preinjury AD was identified as an independent predictor of mortality, but not a predictor of WOC.

CONCLUSION

Despite a high WOC rate in patients older than 65 years, most patients did not have an AD prior to injury. As the elderly trauma population grows, advance care planning should be better integrated into geriatric care to encourage a patient-centered approach to end-of-life care.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level IV.
Paradigms in chronic subdural hematoma pathophysiology: Current treatments and new directions
Authors: Bounajem Michael T. , Campbell Robert A. , Denorme Frederik , Grandhi Ramesh
Published: September 2021

Chronic subdural hematomas (CSDHs) are an increasingly common pathology encountered in a neurosurgical trauma practice. Although the operative and nonoperative management of CSDH has been studied extensively, the recurrence rate of CSDH remains high, with no significant decrease in recent years. We undertook a detailed assessment of the known pathophysiological mechanisms by which CSDHs recur to improve our ability to treat patients with this disease successfully. In this review of the literature from the PubMed and Scopus databases, we used the search terms “(pathophysiology) AND chronic subdural hematoma [tiab]” to identify pertinent reviews and articles in English. The results demonstrated a complex inflammatory response to subdural blood, which begins with the formation of a collagen neomembrane around the clot itself. Proinflammatory mediators, such as vascular endothelial growth factor, interleukin-6, interleukin-8, tissue necrosis factor α, matrix metalloproteinases, and basic fibroblast growth factor, then contribute to chronic microbleeding by promoting the formation of fragile, leaky blood vessels, and widening of gap junctions of existing vessels. It is evident that the lack of improvement in recurrence rate is due to pathological factors that are not entirely alleviated by simple subdural evacuation. Targeted approaches, such as middle meningeal artery embolization and anti-inflammatory therapies, have become increasingly common and require further prospective analysis to aid in the determination of their efficacy.
Evaluation and management of traumatic pneumothorax: A Western Trauma Association critical decisions algorithm
Authors: de Moya Marc , Brasel Karen J. , Brown Carlos V.R. , Hartwell Jennifer L. , Inaba Kenji , Ley Eric J. , Moore Ernest E. , Peck Kimberly A. , Rizzo Anne G. , Rosen Nelson G. , Sperry Jason , Weinberg Jordan A. , Martin Matthew J.
Published: September 2021

This is a recommended algorithm of the Western Trauma Association for the management of a traumatic pneumothorax. The current algorithm and recommendations are based on available published prospective cohort, observational, and retrospective studies and the expert opinion of the Western Trauma Association members. The algorithm and accompanying text represents a safe and reasonable approach to this common problem. We recognize that there may be variability in decision making, local resources, institutional consensus, and patient-specific factors that may require deviation from the algorithm presented. This annotated algorithm is meant to serve as a basis from which protocols at individual institutions can be developed or serve as a quick bedside reference for clinicians.

LEVEL OF EVIDENCE

Consensus algorithm from the Western Trauma Association, Level V.
Not as simple as ABC: Tools to trigger massive transfusion in pediatric trauma
Authors: Phillips Ryan , Shahi Niti , Acker Shannon N. , Meier Maxene , Shirek Gabrielle , Stevens Jenny , Recicar John , Moulton Steven , Bensard Denis
Published: September 2021

BACKGROUND

Early and accurate identification of pediatric trauma patients who will receive massive transfusion (MT) is not well established. We developed the ABCD (defined as penetrating mechanism, positive focused assessment with sonography for trauma, shock index, pediatric age-adjusted [SIPA], lactate, and base deficit [BD]) and BIS scores (defined as a combination of BD, international normalized ratio [INR], and SIPA) and hypothesized that the BIS score would perform best in the ability to predict the need for MT in children.

METHODS

Pediatric trauma patients (≤18 years old) admitted to our trauma center between 2008 and 2019 were identified. Using a receiver operator curve, we defined cutoff points for lactate (≥3.2), BD (≤−6.9), and INR (≥1.4). ABCD scores were calculated by combining penetrating mechanism; positive focused assessment with sonography for trauma examination; SIPA; lactate; and BD. BIS scores were calculated by combining BD, INR, and SIPA. The sensitivity, specificity, and accuracy of each score were calculated based on receiving MT.

RESULTS

Seven hundred seventy-two patients were included, of which 59 (7.6%) underwent MT. The best predictor of receiving MT was achieved by a BIS score of ≥2 that was 98% sensitive and 23% specific with an area under the curve of 0.81. The ABCD score of ≥2 was 97% sensitive and 20% specific with an area under the curve of 0.77.

CONCLUSION

The BIS score, which takes into account derangements in acidosis, coagulopathy, and SIPA, is accurate and easy to perform and can be incorporated into a simple bedside screening tool for triggering MT in pediatric trauma patients.

LEVEL OF EVIDENCE

Diagnostic Tests or Criteria, Level IV.
Living Donor Versus Deceased Donor Pediatric Liver Transplantation: A Systematic Review and Meta-analysis
Authors: Barbetta Arianna , Butler Chanté , Barhouma Sarah , Hogen Rachel , Rocque Brittany , Goldbeck Cameron , Schilperoort Hannah , Meeberg Glenda , Shapiro James , Kwon Yong K. , Kohli Rohit , Emamaullee Juliet
Published: September 2021

Background.

Reduced-size deceased donors and living donor liver transplantation (LDLT) can address the organ shortage for pediatric liver transplant candidates, but concerns regarding technical challenges and the risk of complications using these grafts have been raised. The aim of this study was to compare outcomes for pediatric LDLT and deceased donor liver transplantation (DDLT) via systematic review.

Methods.

A systematic literature search was performed to identify studies reporting outcomes of pediatric (<18 y) LDLT and DDLT published between 2005 and 2019. A meta-analysis was conducted to examine peri- and postoperative outcomes using fixed- and random-effects models.

Results.

Overall, 2518 abstracts were screened, and 10 studies met criteria for inclusion. In total, 1622 LDLT and 6326 DDLT pediatric patients from 4 continents were examined. LDLT resulted in superior patient survival when compared with DDLT at 1, 3, and 5 y post-LT (1-y hazard ratio: 0.58, 95% confidence interval [CI] 0.47-0.73, P < 0.0001). Similarly, LDLT resulted in superior graft survival at all time points post-LT when compared with DDLT (1-y hazard ratio: 0.56 [95% CI 0.46-0.68], P < 0.0001]. The OR for vascular complications was 0.73 (95% CI 0.39-1.39) and 1.31 (95% CI 0.92-1.86) for biliary complications in LDLT compared with DDLT, whereas LDLT was associated with lower rates of rejection (OR: 0.66 [95% CI 0.45-0.96], P = 0.03).

Conclusions.

This meta-analysis demonstrates that LDLT may offer many advantages when compared with DDLT in children and suggests that LDLT should continue to be expanded to optimize outcomes for pediatric LT candidates.
Comanagement With Nephrologist Care Is Associated With Fewer Cardiovascular Events Among Liver Transplant Recipients With Chronic Kidney Disease
Authors: Campbell Patrick T. , Kosirog Megan , Aghaulor Blessing , Gregory Dyanna , Pine Stewart , Daud Amna , Das Arighno , Finn Daniel J. , Levitsky Josh , Holl Jane L. , Lloyd-Jones Donald M. , VanWagner Lisa B.
Published: September 2021

Background.

Chronic kidney disease (CKD) is associated with cardiovascular (CV) events, a leading complication in liver transplant recipients (LTRs). Timely subspecialty care is associated with improved clinical outcomes in patients with CKD. This study sought to assess associations between nephrology comanagement and CV events among LTRs at risk for or with CKD.

Methods.

LTRs with CKD plus those at risk were identified in an inception cohort at a single tertiary care network between 2010 and 2016, using electronic health record data and manual chart review. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or International Classification of Diseases 9th or 10th revision code for CKD and at-risk CKD as estimated glomerular filtration rate 60–89 mL/min/1.73 m2. Cox proportional hazard models assessed the association between nephrology comanagement and CV events among LTRs with or at risk for CKD.

Results.

Among 602 LTRs followed for up to 6 y posttransplant, prevalence of CKD plus those at risk increased yearly (71% in year 1, 86% in year 6) (P < 0.0001). Rates of nephrology comanagement decreased yearly posttransplant (35% in year 1, 28% in year 6). In multivariable models, nephrology comanagement was associated with lower CV events (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33–0.99).

Conclusions.

Among LTRs with CKD, nephrology comanagement may be associated with lower CV events. A prospective study is needed to identify the reasons for improved outcomes and barriers to nephrology referral.
Liver Transplantation With Grafts From Super Obese Donors
Authors: Vargas Paola A. , Cullen J. Michael , Argo Curtis , Henry Zachary , Stotts Matthew J. , Intagliata Nicolas , Northup Patrick , Oberholzer Jose , Pelletier Shawn , Goldaracena Nicolas
Published: September 2021

Background.

There are limited data on liver transplant (LT) outcomes with grafts from super obese donors. The present study aims to evaluate a unique cohort of recipients following LT using grafts from donors with body mass index (BMI) ≥50.

Methods.

Patients receiving grafts from donors with BMI ≥50 and BMI <50 from 2010 to 2019 were identified. A 1:2 case–control match was conducted to compare outcomes between the groups. Survival was analyzed using the Kaplan-Meier curves.

Results.

Six hundred sixty-five adult LTs were performed in the study period. Eighteen patients receiving a graft from a donor with BMI ≥50 were identified and matched to 36 patients receiving a graft from a donor with BMI <50. Grafts from male donors were significantly lower in the donor BMI ≥50 group when compared with the donor BMI <50 group (16.7% versus 66.7%, P = 0.001). Liver biopsy was performed in 77.8% of grafts in the donor BMI ≥50 group, whereas only in 38.8% of the grafts in the donor BMI <50 group (P = 0.007). Recipients in the donor BMI ≥50 group had a significantly higher diagnosis rate of hepatocellular carcinoma pretransplant versus the donor BMI <50 group (38.9% versus 8.3%, respectively; P = 0.006). Major complications within 30 d did not differ statistically between groups. Biliary complications within the first 30 d were equal among groups (16.7%). Subanalysis comparing the super obese donor group versus the nonobese donor group showed no differences in terms of postoperative complications, readmission rate, graft rejection, or major complications including the need for reoperation, retransplantation, or mortality. Graft and patient survival at 1-, 3-, and 5-y graft were similar between the donor BMI ≥50 group versus donor BMI <50 group (94%/89%/89% versus 88%/88%/88%, P = 0.89, and 94%/94%/94% versus 88%/88%/88%, P = 0.48, respectively).

Conclusions.

LT with carefully selected grafts from super obese donors can be safely performed with outcomes comparable with non–super obese donor livers. Therefore, these types of grafts could represent a safe means to expand the donor pool.
Exploring the utility of current polygenic scores in capturing resilience
Authors: Bucknor Brianna A. , Derringer Jaime
Published: September 2021

Although resilience has been identified to be moderately heritable, little is known about the genetic variants involved. While there has not yet been a robust genome-wide association study (GWAS) of resilience, existing GWAS of related phenotypes may provide a starting point for developing our understanding of the heritability of resilience. In a sample of older, US adults (N = 9480), we examined the extent to which proxy polygenic scores (PGS) explained the variance in resilience. Four of the 32 PGS assessed (subjective wellbeing, neuroticism, depressive symptoms and educational attainment) reached significance among participants with European ancestries, but with relatively small effects (

= 0.002–0.09). Notably, PGSs derived from GWAS of PTSD among participants with either European or African ancestries were uncorrelated with resilience. Even aggregated across all available proxy PGSs, existing PGSs are not sufficient to inform our understanding of the genetics underlying the heritability of resilience. A large-scale GWAS of resilience is needed as it would provide greater insight into the genetic mechanisms underlying the heritability of resilience.
Towards a phylogenetic ecology of plant pests and pathogens
Authors: Gougherty Andrew V. , Davies T. Jonathan
Published: September 2021

Plant–pathogens and insect pests, hereafter pests, play an important role in structuring ecological communities, yet both native and introduced pests impose significant pressure on wild and managed systems, and pose a threat to food security. Global changes in climate and land use, and transportation of plants and pests around the globe are likely to further increase the range, frequency and severity of pest outbreaks in the future. Thus, there is a critical need to expand on current ecological theory to address these challenges. Here, we outline a phylogenetic framework for the study of plant and pest interactions. In plants, a growing body of work has suggested that evolutionary relatedness, phylogeny, strongly structures plant-pest associations—from pest host breadths and impacts, to their establishment and spread in new regions. Understanding the phylogenetic dimensions of plant-pest associations will help to inform models of invasive species spread, disease and pest risk in crops, and emerging pest outbreaks in native plant communities—which will have important implications for protecting food security and biodiversity into the future.

This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.
Spatial variation in species' roles in host–helminth networks
Authors: Dallas Tad A. , Jordano Pedro
Published: September 2021

Species interactions may vary considerably across space as a result of spatial and environmental gradients. With respect to host–parasite interactions, this suggests that host and parasite species may play different functional roles across the different networks they occur in. Using a global occurrence database of helminth parasites, we examine the conservation of species' roles using data on host–helminth interactions from 299 geopolitical locations. Defining species' roles in a two-dimensional space which captures the tendency of species to be more densely linked within species subgroups than between subgroups, we quantified species' roles in two ways, which captured
if
and
which
species' roles are conserved by treating species' utilization of this two-dimensional space as continuous, while also classifying species into categorical roles. Both approaches failed to detect the conservation of species' roles for a single species out of over 38 000 host and helminth parasite species. Together, our findings suggest that species' roles in host–helminth networks may not be conserved, pointing to the potential role of spatial and environmental gradients, as well as the importance of the context of the local host and helminth parasite community.

This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.
Functional biogeography of parasite traits: hypotheses and evidence
Authors: Poulin Robert
Published: September 2021

Functional biogeography, or the study of trait-based distributional patterns, not only complements our understanding of spatial patterns in biodiversity, but also sheds light on the underlying processes generating them. In parallel with the well-studied latitudinal diversity gradient, decades-old ecogeographical rules also postulate latitudinal variation in species traits. Notably, species in the tropics are predicted to have smaller body sizes (Bergmann's rule), narrower niches (MacArthur's rule) and smaller geographical ranges (Rapoport's rule) than their counterparts at higher latitudes. Although originally proposed for free-living organisms, these rules have been extended to parasitic organisms as well. In this review, I discuss the mechanistic hypotheses most likely to explain latitudinal gradients in parasite traits, and assess the empirical evidence obtained from comparative studies testing the above three rules as well as latitudinal gradients in other parasite traits. Overall, there is only weak empirical support for latitudinal gradients in any parasite trait, with little consistency among comparative analyses. The most parsimonious explanation for the existence of geographical patterns in parasite traits is that they are primarily host-driven, i.e. ecological traits of parasites track those of their hosts, with a direct influence of bioclimatic factors playing a secondary role. Thus, geographical patterns in parasite traits probably emerge as epiphenomena of parallel patterns in their hosts.

This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.
A roadmap towards predicting species interaction networks (across space and time)
Authors: Strydom Tanya , Catchen Michael D. , Banville Francis , Caron Dominique , Dansereau Gabriel , Desjardins-Proulx Philippe , Forero-Muñoz Norma R. , Higino Gracielle , Mercier Benjamin , Gonzalez Andrew , Gravel Dominique , Pollock Laura , Poisot Timothée
Published: September 2021

Networks of species interactions underpin numerous ecosystem processes, but comprehensively sampling these interactions is difficult. Interactions intrinsically vary across space and time, and given the number of species that compose ecological communities, it can be tough to distinguish between a true negative (where two species never interact) from a false negative (where two species have not been observed interacting even though they actually do). Assessing the likelihood of interactions between species is an imperative for several fields of ecology. This means that to predict interactions between species—and to describe the structure, variation, and change of the ecological networks they form—we need to rely on modelling tools. Here, we provide a proof-of-concept, where we show how a simple neural network model makes accurate predictions about species interactions given limited data. We then assess the challenges and opportunities associated with improving interaction predictions, and provide a conceptual roadmap forward towards predictive models of ecological networks that is explicitly spatial and temporal. We conclude with a brief primer on the relevant methods and tools needed to start building these models, which we hope will guide this research programme forward.

This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.
The genomes of nucleocytoplasmic large DNA viruses: viral evolution writ large
Authors: Mönttinen Heli A. M. , Bicep Cedric , Williams Tom A. , Hirt Robert P.
Published: September 2021

The nucleocytoplasmic large DNA viruses (NCLDVs) are a diverse group that currently contain the largest known virions and genomes, also called giant viruses. The first giant virus was isolated and described nearly 20 years ago. Their genome sizes were larger than for any other known virus at the time and it contained a number of genes that had not been previously described in any virus. The origin and evolution of these unusually complex viruses has been puzzling, and various mechanisms have been put forward to explain how some NCLDVs could have reached genome sizes and coding capacity overlapping with those of cellular microbes. Here we critically discuss the evidence and arguments on this topic. We have also updated and systematically reanalysed protein families of the NCLDVs to further study their origin and evolution. Our analyses further highlight the small number of widely shared genes and extreme genomic plasticity among NCLDVs that are shaped via combinations of gene duplications, deletions, lateral gene transfers and de novo creation of protein-coding genes. The dramatic expansions of the genome size and protein-coding gene capacity characteristic of some NCLDVs is now increasingly understood to be driven by environmental factors rather than reflecting relationships to an ancient common ancestor among a hypothetical cellular lineage. Thus, the evolution of NCLDVs is writ large viral, and their origin, like all other viral lineages, remains unknown.
Colony-like Protocell Superstructures
Authors: Spustova Karolina , Katke Chinmay , Pedrueza Villalmanzo Esteban , Ryskulov Ruslan , Kaplan C. Nadir , Gözen Irep
Published: September 2021

We report the formation, growth, and dynamics of model protocell superstructures on solid surfaces, resembling single cell colonies. These structures, consisting of several layers of lipidic compartments enveloped in a dome-shaped outer lipid bilayer, emerged as a result of spontaneous shape transformation of lipid agglomerates deposited on thin film aluminum surfaces. Collective protocell structures were observed to be mechanically more stable compared to isolated spherical compartments. We show that the model colonies encapsulate DNA and accommodate non-enzymatic, strand displacement DNA reactions. The membrane envelope is able to disassemble and expose individual daughter protocells, which can migrate and attach via nano-tethers to distant surface locations, while maintaining their encapsulated contents. Some colonies feature ‘exo-compartments’, which spontaneously extend out of the enveloping bilayer, internalize DNA, and merge again with the superstructure. A continuum elastohydrodynamic theory that we developed reveals that the subcompartment formation must be governed by attractive van der Waals (vdW) interactions between the membrane and surface. The balance between membrane bending and vdW interactions yields a critical length scale of 273 nm, above which the membrane invaginations can form subcompartments. The findings support our hypotheses that in extension of the ‘lipid world hypothesis’, protocells may have existed in the form of colonies, potentially benefiting from the increased mechanical stability provided by a superstructure.
A Taphrina strain infecting the model plant Arabidopsis thaliana
Authors: Christita Margaretta , Auzane Agate , Wang Kai , Sipilä Timo , Auvinen Petri , Paulin Lars , Salojärvi Jarkko , Overmyer Kirk
Published: September 2021

Yeasts are important plant-associated organisms that can modulate host immunity to either promote or prevent disease. Mechanisms of plant-yeast interactions, specifically of yeast perception by the plant innate immune system, remain unknown. Progress has been hindered by the scarcity of yeast species associated with the model plant Arabidopsis thaliana (Arabidopsis). We have previously isolated Taphrina strain M11 from wild Arabidopsis in the field. Taphrina are poorly studied dimorphic yeast-like fungi that are plant pathogens, often producing plant hormones and causing tumour-like and leaf deformation symptoms on their hosts. Here we characterize the interaction of M11 with Arabidopsis. Infection of Arabidopsis with the birch pathogen T. betulina, used as a non-host control, shows early HR, enhanced ROS accumulation, and limitation of growth, demonstrating that Arabidopsis had immunity against non-adapted yeasts. M11 triggered limited cell death, an attenuated ROS response, and grew in planta, as well as subtle but clear leaf deformation symptoms, demonstrating it is pathogenic. Hormone responsive promoter-reporter analysis demonstrated activation of cytokinin signalling during infection. Mutant infection assays indicate jasmonate and ethylene were required for immunity against M11. Analysis of the Taphrina M11 genome was used to mine evidence for yeast specific PAMPs which may underlie host immune responses against yeast-like fungi.
Reactivating Hippocampal-Mediated Memories During Reconsolidation to Disrupt Fear
Authors: Grella Stephanie L. , Fortin Amanda H. , Ruesch Evan , Bladon John H. , Reynolds Leanna F. , Gross Abby , Shpokayte Monika , Cincotta Christine , Zaki Yosif , Ramirez Steve
Published: September 2021

Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system in mice, we label dorsal dentate gyrus neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells are artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory is sufficient to update the memory during reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrate operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While memory-updating, induced by memory reactivation, involves a relatively small set of neurons, we also find that activating a large population of randomly labeled dorsal dentate gyrus neurons is effective in promoting reconsolidation. Importantly, memory-updating is specific to the fear memory. These findings implicate the dorsal dentate gyrus as a potential therapeutic node for modulating memories to suppress fear.
Experimental and computational analysis of calcium dynamics in 22q11.2 deletion model astrocytes
Authors: Maly Ivan V. , Hofmann Wilma A. , Pletnikov Mikhail V.
Published: September 2021

Intracellular calcium dynamics in spontaneously active cells such as neurons or astrocytes is an information-rich readout of the physiological state of the cell. Methods for deriving mechanistic information from biological time courses, as well as for algorithmically extracting cellular activity time courses from imaging data, have significantly advanced in recent years but been mostly applied to neuronal data. At the same time, the role for astrocytes, a type of glial brain cells, in cognition and psychiatric diseases remains poorly understood. Using calcium imaging, computer vision, and Bayesian kinetic inference, we analyze calcium dynamics in primary astrocytes derived from control orDf1/+ mice, a model of 22q11.2 deletion syndrome (DiGeorge syndrome). Inference of highest-likelihood molecular kinetic characteristics from the intracellular calcium time courses pinpoints a significant change in the activity of the sarcoendoplasmic reticulum calcium ATPase (SERCA). Applying a SERCA inhibitor to the control cells reproduces the differences detected in the deletion-bearing cells. Our work identifies for the first time the molecular changes driving the calcium kinetics in 22q11.2 deletion model astrocytes. We conclude that Bayesian kinetic inference is a useful tool for mechanistic dissection of a complex cellular phenotype, calcium dynamics, in glial cells. This method has the potential to facilitate formulation of specific hypotheses concerning the underlying molecular mechanisms, prioritization of experiments testing such hypotheses, and, in the future, individualized functional molecular diagnostics.
Gene flow between two thick-billed grasswren subspecies with low dispersal creates a genomic pattern of isolation-by-distance
Authors: Slender Amy L. , Louter Marina , Myers Steven A. , Bradford Tessa , Gardner Michael G. , Kleindorfer Sonia
Published: September 2021

Context

In the era of the Anthropocene, habitat loss and environmental change threaten the persistence of many species. Genotyping-By-Sequencing (GBS) is a useful molecular tool for understanding how patterns of gene flow are associated with contemporary habitat distributions that may be affected by environmental change. Two parapatric subspecies of the threatened thick-billed grasswren (TBGW; Amytornis modestus) more frequently occur in different plant communities. As such, a preference for plant community type could reduce subspecific introgression and increase genetic diversity at the parapatric boundary.

Aims

We aimed to measure gene flow within and among two TBGW subspecies and tested whether divergent genomic markers were associated with plant community type.

Methods

We sequenced 118 individuals from either of the two TBGW subspecies or in the region of parapatry and identified 7583 SNPs through ddRADseq.

Key results

We found evidence of asymmetric gene flow and a genomic pattern of isolation-by-distance. There were sixteen genomic outliers correlated with plant community type (regardless of location).

Conclusions

These findings show that plant community type does not prevent introgression in one subspecies (A. m. raglessi), but low dispersal and habitat heterogeneity could contribute to the maintenance of distinct subspecific morphotypes. Local adaptation in different plant community types could also provide a mechanism for future divergence.

Implications

We suggest subspecific introgression could increase genetic variation and the adaptive potential of the species, facilitating species persistence under conditions of climate change.

Introgression between grasswren subspecies

Characterising gene flow facilitates conservation management. This study used genomic markers to measure gene flow between thick-billed grasswren subspecies and found results that support taxonomic identification of the two subspecies and suggests grasswrens have low dispersal and may benefit from increased genetic diversity. Recognition of models of divergence with gene flow will be necessary for future conservation management.
Context-dependence in the symbiosis between Dictyostelium discoideum and Paraburkholderia
Authors: Scott Trey J. , Queller David C. , Strassmann Joan E.
Published: September 2021

Symbiotic interactions change with environmental context. Measuring these context-dependent effects in hosts and symbionts is critical to determining the nature of symbiotic interactions. We investigated context-dependence in the symbiosis between social amoeba hosts and their inedible Paraburkholderia bacterial symbionts, where the context is the abundance of host food bacteria. Paraburkholderia have been shown to harm hosts dispersed to food-rich environments, but aid hosts dispersed to food-poor environments by allowing hosts to carry food bacteria. Through measuring symbiont density and host spore production, we show that this food context matters in three other ways. First, it matters for symbionts, who suffer a greater cost from competition with food bacteria in the food-rich context. Second, it matters for host-symbiont conflict, changing how symbiont density negatively impacts host spore production. Third, data-based simulations show that symbiosis often provides a long-term fitness advantage for hosts after rounds of growth and dispersal in variable food-contexts, especially when conditions are harsh with little food. These results show how food context can have many consequences for the Dictyostelium-Paraburkholderia symbiosis and that both sides can frequently benefit.

Impact Statement

Many organisms form symbiotic relationships with other species. These symbioses often exhibit context-dependence, where the sign or magnitude of one partner’s effect on the other will change in different environments. Context-dependent effects make it difficult to assign interactions to categories like mutualisms or antagonisms because they involve both benefits and costs depending on the environment. However, in some cases, accounting for context-dependence can clarify an interaction so that it more easily fits a mutualism or antagonism. We investigated context-dependence using the symbiosis between Dictyostelium discoideum and two symbiotic Paraburkholderia species. In this symbiosis, Paraburkholderia bacteria allow hosts to carry food bacteria to food-poor contexts, where hosts rarely survive without food, but reduce host fitness in the more hospitable food-rich contexts. The effect of food context on Paraburkholderia symbionts is unknown. We show that Paraburkholderia symbionts are also affected by this context, through facing reduced competition after being dispersed by hosts to food-poor contexts. We also identify a new way that symbionts affect hosts, where symbiont density reduces host fitness, but less so in food-poor contexts. Finally, we use simulations to show that infected hosts benefit in the long-term across variable food contexts, especially in the harshest environments with little food. These results show that context-dependence in symbiosis can have many consequences for hosts and symbionts, though in general for D. discoideum and Paraburkholderia, both are likely to benefit.
Towards Compilation of Balanced Protein Stability Datasets: Flattening the ΔΔG Curve through Systematic Under-sampling
Authors: Kebabci Narod , Timucin Ahmet Can , Timucin Emel
Published: September 2021

Protein stability datasets contain neutral mutations that are highly concentrated in a much narrower ΔΔG range than destabilizing and stabilizing mutations. Notwith-standing their high density, often studies analyzing stability datasets and/or predictors ignore the neutral mutations and use a binary classification scheme labeling only destabilizing and stabilizing mutations. Recognizing that highly concentrated neutral mutations would affect the quality of stability datasets, we have explored three protein stability datasets; S2648, PON-tstab and the symmetric Ssymthat differ in size and quality. A characteristic leptokurtic shape in the ΔΔG distributions of all three datasets including the curated and symmetric ones were reported due to concentrated neutral mutations. To further investigate the impact of neutral mutations on ΔΔG predictions, we have comprehensively assessed the performance of eleven predictors on the PON-tstab dataset. Correlation and error analyses showed that all of the predictors performed the best on the neutral mutations while their performance became gradually worse as the ΔΔG of the mutations departed further from the neutral zone regardless of the direction, implying a bias towards dense mutations. To this end, after unraveling the role of concentrated neutral mutations in biases of stability datasets, we described a systematic under-sampling approach to balance the ΔΔG distributions. Before under-sampling, mutations were clustered based on their biochemical and/or structural features and then three mutations were systematically selected from every 2 kcal/mol of each cluster. Upon implementation of this approach by distinct clustering schemes, we generated five subsets varying in size and ΔΔG distributions. All subsets notably showed amelioration of not only the shape of ΔΔG distributions but also other pre-existing imbalances in the frequency distributions. We also reported differences in the performance of the predictors between the parent and under-sampled subsets due to the enrichment of previously under-represented mutations in the subsets. Altogether, this study not only elaborated the pivotal role of concentrated mutations in the dataset biases but also contemplated and realized a rational strategy to tackle this and other forms of biases. Under-sampling code is available on GitHub (https://github.com/narodkebabci/gRoR).
Combining genotypes and T cell receptor distributions to infer genetic loci determining V(D)J recombination probabilities
Authors: Russell Magdalena L , Souquette Aisha , Levine David M , Allen E Kaitlynn , Kuan Guillermina , Simon Noah , Balmaseda Angel , Gordon Aubree , Thomas Paul G , Matsen Frederick A , Bradley Philip
Published: September 2021

Every T cell receptor (TCR) repertoire is shaped by a complex probabilistic tangle of genetically determined biases and immune exposures. T cells combine a random V(D)J recombination process with a selection process to generate highly diverse and functional TCRs. The extent to which an individual’s genetic background is associated with their resulting TCR repertoire diversity has yet to be fully explored. Using a previously published repertoire sequencing dataset paired with high-resolution genome-wide genotyping from a large human cohort, we infer specific genetic loci associated with V(D)J recombination probabilities using genome-wide association inference. We show that V(D)J gene usage profiles are associated with variation in theTCRBlocus and, specifically for the functional TCR repertoire, variation in the major histocompatibility complex locus. Further, we identify specific variations in the genes encoding the Artemis protein and the TdT protein to be associated with biasing junctional nucleotide deletion and N-insertion, respectively. These results refine our understanding of genetically-determined TCR repertoire biases by confirming and extending previous studies on the genetic determinants of V(D)J gene usage and providing the first examples oftransgenetic variants which are associated with modifying junctional diversity. Together, these insights lay the groundwork for further explorations into how immune responses vary between individuals.
Physical and functional interactome atlas of human receptor tyrosine kinases
Authors: Salokas Kari , Öhman Tiina , Liu Xiaonan , Chowdhury Iftekhar , Gawriyski Lisa , Keskitalo Salla , Varjosalo Markku
Published: September 2021

Much cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite their central roles, the functions of many RTKs are still poorly understood. To resolve the lack of systematic knowledge, we used three complementary methods to map the molecular context and substrate profiles of RTKs. We used affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates. To identify how kinase interactions depend on kinase activity, we also used kinase-deficient mutants. Our data represent a comprehensive, systemic mapping of RTK interactions and substrates. This resource adds information regarding well-studied RTKs, offers insights into the functions of less well-studied RTKs, and highlights RTK-RTK interactions and shared signaling pathways.
Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes
Authors: Calia Andrea Bonaccini , Masvidal-Codina Eduard , Smith Trevor M. , Schäfer Nathan , Rathore Daman , Rodríguez-Lucas Elisa , Illa Xavi , De la Cruz Jose M. , Del Corro Elena , Prats-Alfonso Elisabet , Viana Damià , Bousquet Jessica , Hébert Clement , Martínez-Aguilar Javier , Sperling Justin R. , Drummond Matthew , Halder Arnab , Dodd Abbie , Barr Katharine , Savage Sinead , Fornell Jordina , Sort Jordi , Guger Christoph , Villa Rosa , Kostarelos Kostas , Wykes Rob , Guimerà-Brunet Anton , Garrido Jose A.
Published: September 2021

Mapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.
Evolutionary history of an Alpine archaeognath (Machilis pallida) – insights from different variant types
Authors: Haider Marlene , Schilling Martin P. , Moest Markus H. , Steiner Florian M. , Schlick-Steiner Birgit C. , Arthofer Wolfgang
Published: September 2021

Reconstruction of species histories is a central aspect of evolutionary biology. Patterns of genetic variation within and among populations can be leveraged to elucidate evolutionary processes and demographic histories. However, interpreting genetic signatures and unraveling the contributing processes can be challenging, in particular for non-model organisms with complex reproductive modes and genome organization. One way forward is the combined consideration of patterns revealed by different molecular markers (nuclear vs. mitochondrial) and types of variants (common vs. rare) that differ in their age, mode and rate of evolution. Here, we applied this approach to Machilis pallida (Archaeognatha), an Alpine jumping bristletail considered parthenogenetic and triploid. We generated de-novo transcriptome and mitochondrial assemblies to obtain high-density data to investigate patterns of mitochondrial and common and rare nuclear variation in 17 M. pallida individuals sampled across the Alps from all known populations. We find that the different variant types capture distinct aspects of the evolutionary history and discuss the observed patterns in the context of parthenogenesis, polyploidy and survival during glaciation. This study highlights the potential of different variant types to unravel complex evolutionary scenarios and the suitability of M. pallida and the genus Machilis as a study system for the evolution of sexual strategies and polyploidization during environmental change. We also emphasize the need for further research which will be stimulated and facilitated by these newly generated resources and insights.