bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mediational Analysis of Stress, Inflammation, Sleep, and Pain in Acute Musculoskeletal Trauma
Authors: Walton David M. , Pourkazemi Fareshteh , Ghodrati Maryam , Elliott James M.
Published: December 2019

Objectives:

Differences in pain severity among acutely injured people may be related to the perceived stress of the event and pre-existing vulnerabilities. In this study, we test the hypotheses that pretrauma life stress influences posttrauma pain severity, and 2 potential mediating pathways, 1 biological (C-reactive protein, CRP) and 1 contextual (sleep quality).

Materials and Methods:

Data collected from participants within 3 weeks of a noncatastrophic musculoskeletal trauma were used in this observational cross-sectional mediation analysis. The primary outcome was pain severity as measured using the Brief Pain Inventory. Predictors were posttrauma CRP assayed from plasma, sleep interference measured by the Brief Pain Inventory, and a study-specific “General Life Stressors” scale. First, the sample was split into low and high life-stress groups, and mean differences in the pain and the predictor variables were explored by t test. Next, a mediation model was tested through a regression-based path analysis. The base model explored the predictive association between pretrauma life stress and posttrauma pain. Sleep quality and CRP concentration were then entered as possible mediators of the association.

Results:

The sample of 112 participants was 54.6% female, and 52.7% reported high pretrauma life stress. Mean differences in pain severity, sleep interference, and CRP was significant between the high-stress and low-stress groups. In path analysis, life stress explained 8.0% of the variance in acute pain severity, 6.3% of the variance in sleep interference, and 8.0% of the variance in CRP concentration, all P-value <0.05. In mediation analysis, the association between life stress and pain severity was fully mediated by sleep interference. CRP did not mediate the association.

Discussion:

Pretrauma life stress predicted pain severity, sleep interference, and plasma CRP. In mediation analysis, pretrauma stress was associated with pain severity only through its association with sleep interference, while CRP did not mediate the association. Implications of these results are discussed.
HASPIN kinase inhibitor CHR-6494 suppresses intestinal polyp development, cachexia, and hypogonadism in Apc min/+ mice
Authors: Tanaka Hiromitsu , Wada Morimasa , Park Junhyeok
Published: December 2019

HASPIN has been identified as a nuclear Ser/Thr kinase specifically expressed in haploid germ cells. HASPIN kinase inhibitors were recently isolated, and their antitumor activity reported. Colorectal cancer occurs with high incidence worldwide. In this study, we examined whether HASPIN inhibitor CHR-6494 suppresses cancer progression in Apc

Min/+
mice, a familial colon tumor disease model. Mice were treated by intraperitoneal injection of CHR-6494 for 50 days. Following the treatment period, intestinal polyps were counted and testosterone and spermatogenesis levels were observed. Intraperitoneal administration of CHR-6494 significantly inhibited intestinal polyp development and recovered body weight in Apc

Min/+
mice. Although spermatogenesis was inhibited with increasing age in Apc

Min/+ mice, CHR-6494 significantly improved blood testosterone levels and spermatogenesis. Our results suggest that HASPIN inhibitors may be useful as anti-cancer agents and for the treatment of hypogonadism in colorectal cancer patients.
Comparison of chemotherapy effects on mechanical sensitivity and food-maintained operant responding in male and female rats
Authors: Legakis Luke P. , Diester Clare M. , Townsend Edward A. , Karim-Nejad Ladan , Negus Sidney Stevens
Published: December 2019

Chemotherapies of varying classes often cause neuropathy and debilitating chemotherapy-induced neuropathic pain sufficient to limit treatment and reduce quality of life for many patients battling cancer. There are currently no effective preventive or alleviative treatments for chemotherapy-induced neuropathic pain. Preclinical models have been developed to test candidate chemotherapy-induced neuropathic pain treatments; however, studies using these models rarely provide direct comparisons of effects of different chemotherapies or assess the degree to which chemotherapies produce clinically relevant signs of pain-depressed behavior. Male and female Sprague–Dawley rats received four injections of vehicle, paclitaxel, oxaliplatin, vincristine, or bortezomib on alternate days. Mechanical hypersensitivity, body weight, and food-maintained operant responding were evaluated before, during, and for up to 42 days after initiation of treatment. Morphine potency and effectiveness to reverse chemotherapy-induced effects were also evaluated. All four chemotherapies produced dose-dependent and sustained mechanical hypersensitivity in all rats. Vincristine and oxaliplatin produced transient weight loss and decreases in food-maintained operant responding in all rats, whereas paclitaxel and bortezomib produced lesser or no effect. At 4 weeks after treatment, operant responding was depressed only in paclitaxel-treated males. Morphine reversed mechanical hypersensitivity in all rats but failed to reverse paclitaxel-induced depression of operant responding in males. We conclude that chemotherapy treatments sufficient to produce sustained mechanical hypersensitivity failed to produce sustained or morphine-reversible behavioral depression in rats. Insofar as pain-related behavioral depression is a cardinal sign of chemotherapy-induced neuropathic pain in humans, these results challenge the presumption that these chemotherapy-dosing regimens are sufficient to model clinically relevant chemotherapy-induced neuropathic pain in rats.
Do Bundled Payment Programs in Joint Replacement Care Hold Promise for Improving Patient Outcomes?
Authors: Lassen Tobin , Revere Lee , Hailemariam Desta , Hogan Patrick J. , Hernandez Eduardo
Published: December 2019

The Centers for Medicare and Medicaid Services (CMS) Innovation Center offers two alternative payment models for joint replacement: the voluntary Bundled Payment for Care Improvement (BPCI) model and the mandatory Comprehensive Care for Joint Replacement (CJR) model. As CMS considers methods for cost reduction, research is needed to understand patient-level outcomes and organizational-level success factors. A retrospective cross-sectional study of hospitals was performed, using regression models to evaluate an aggregate patient satisfaction score, complication rates, and operational differences among BPCI, CJR, and nonparticipating hospitals. Results show that BPCI hospitals received significantly better patient satisfaction scores (88.6) than CJR hospitals (86.0), but complication rates were not significantly different between CJR and BPCI hospitals (2.83 and 2.77, respectively). Factors associated with BPCI participation include academic affiliation, a Northeast region locale, and having a higher CMS efficiency score. Thus, requiring more hospitals to participate in CMS-bundled payment programs as a federal policy may not be the optimal way to improve patient satisfaction and outcomes. Rather, the CJR and BPCI programs should be further studied, and the results generalized for use by nonparticipating hospitals to encourage preparation and participation in CMS value-based initiatives.
Analysis of #PlasticSurgery in Europe: An Opportunity for Education and Leadership
Authors: Maldonado Andrés A. , Lemelman Benjamin T. , Le Hanneur Malo , Coelho Ruben , Cristóbal Lara , Sader Robert , Sauerbier Michael
Published: December 2019

Background:

Prior studies demonstrate that social media are used by plastic surgeons to educate and engage. The hashtag #PlasticSurgery has been studied previously and is embraced by American plastic surgeons and journals; however, no studies have examined its use or adoption across Europe.

Methods:

A retrospective analysis of 800 tweets containing the words “plastic surgery” or the hashtag #PlasticSurgery in four of the most spoken European languages worldwide excluding English (Spanish, #CirugiaPlastica; French, #ChirurgiePlastique; Portuguese, #CirurgiaPlastica; and German, #PlastischeChirurgie) was performed. The following were assessed: identity of author, subject matter, use of the hashtag #PlasticSurgery in each language, whether posts by surgeons and academic institutions were self-promotional or educational, and whether a link to a journal article or a reference in PubMed was provided.

Results:

Seventeen percent and 3 percent of analyzed tweets came from plastic surgeons or academic institutions, respectively; only 17.5 percent of them were for educational purpose. None of them had any digital link to a peer-reviewed article or a scientific journal.

Conclusions:

This study demonstrates the low participation of plastic surgeons and academic institutions in social media (especially for education) in four of the major world languages. Social media should be considered in Europe as an opportunity to increase leadership, improve education, and spread knowledge of plastic surgery by board-certified plastic surgeons.
Mapping Psilocybin-Assisted Therapies: A Scoping Review
Authors: Shore Ron , Ioudovski Paul , Goldie Craig , McKeown Sandra , Dumont Eric ,   Queen’s University, Kingston On.
Published: December 2019

We conducted a scoping review on psilocybin-assisted therapy for addiction, depression, anxiety and post-traumatic stress disorder. Psilocybin is a naturally-occurring tryptophan derivative found in species of mushroom with psycho-active properties. From 2022 records identified by database searching, 40 publications were included in the qualitative synthesis from which we identified 9 clinical trials with a total of 169 participants. Trials used a peak-psychedelic model of therapy, emphasizing inward journey through the use of eyeshades, set musical scores and with medium to high doses of psilocybin. No serious adverse effects were reported; mild adverse effects included transient anxiety, nausea and post-treatment headaches. Overall, the 9 trials all demonstrated safety, tolerability and preliminary efficacy in the treatments of obsessive-compulsive disorder, substance use disorder, treatment-resistant unipolar depression, anxiety or depression in patients with life-threatening cancer and demoralization among long-term AIDS survivors.The literature was found to be early and exploratory, with several limitations: only 5 were randomized controlled trials, small and homogenous patient sample size, difficulties in blinding, and the confounding influence of psychological supports provided. Further research is indicated to establish effectiveness for these and other indications, with a more diverse range of patients, and with differing program and dosing modalities.
Population structure and clonal prevalence of scleractinian corals (Montipora capitataandPorites compressa) in Kaneohe Bay, Oahu
Authors: Locatelli NS , Drew JA
Published: December 2019

As the effects of anthropogenic climate change grow, mass coral bleaching events are expected to increase in severity and extent. Much research has focused on the environmental stressors themselves, symbiotic community compositions, and transcriptomics of the coral host. Globally, fine-scale population structure of corals is understudied. This study reports patterns of population structure and clonal prevalence found inMontipora capitataandPorites compressain Kaneohe Bay, Oahu. Generated using ddRAD methods, genetic data reveals different patterns in each taxa despite them being exposed to the same environmental conditions. STRUCTURE and site-level pairwise FSTanalyses suggest population structure inM. capitataresembling isolation by distance. Mantel tests show strong, significant FSTcorrelations inM. capitatain relation to geographic distance, water residence time, and salinity and temperature variability (range) at different time scales. STRUCTURE did not reveal strong population structure inP. compressa.FSTcorrelation was found inP. compressain relation to yearly average sea surface height. We also report high prevalence of clonal colonies inP. compressain outer bay sites exposed to storms and high energy swells. Amongst only outer bay sites, 7 out of 23 sequenced individuals were clones of other colonies. Amongst all 47 sequencedP. compressaindividuals, 8 were clones. Only one clone was detected inM. capitata. Moving forward, it is crucial to consider these preexisting patterns relating to genetic diversity when planning and executing conservation and restoration initiatives. Recognizing that there are differences in population structure and diversity between coral taxa, even on such small-scales, is important as it suggests that small-scale reefs must be managed by species rather than by geography.
Measurements of 3-D morphology of individual red blood cells upon localized photothermal effects using gold nanorods
Authors: Song Chanwoo , Lee Gu-Haeng , Oh Juntaek , Lee Moosung , Shin Seungwoo , Lee SangYun , Nam Yoonkey , Park YongKeun
Published: December 2019

We investigated the in-situ photothermal response of human red blood cells (RBCs) by combining photothermal heat generation and 3-D quantitative phase imaging techniques. Gold-nanorod-coated substrates were excited using near-infrared light to generate local heat to RBCs, and response was measured by imaging 3-D refractive index tomograms of cells under various near infrared (NIR) excitation conditions. On photothermal treatment, cell morphology changed from discoid to crescent shapes, cell volume and dry mass decreased, and hemoglobin concentration increased. We also investigated the irreversible deformation of RBCs when multiple intense excitation shocks are applied. These results provide a new understanding of thermodynamic aspects of cell biology and hematology.
Differential contributions of left-hemispheric language regions to basic semantic composition
Authors: Graessner Astrid , Zaccarella Emiliano , Hartwigsen Gesa
Published: December 2019

Semantic composition, i.e. the ability to combine single words to form complex meanings, is a core feature of human language. Despite growing interest in the basis of semantic composition, the neural correlates and the interaction of regions within this network remain a matter of debate. In the present fMRI study, we designed a well controlled two-word paradigm in which phrases only differed along the semantic dimension while keeping syntactic information alike. 33 healthy participants listened to meaningful phrases (“fresh apple”), anomalous phrases (“awake apple”) and pseudoword phrases (“awake gufel”) while performing both an implicit and an explicit semantic task. We identified neural signatures for distinct processes during basic semantic composition: Thegeneral phrasal compositionprocess, which is independent of the plausibility of the resulting phrase, engages a wide-spread left hemispheric network comprising both executive semantic control regions as well as general conceptual representation regions. Within this network, the functional connectivity between the left anterior inferior frontal gyrus, the bilateral pre-supplementary motor area and the posterior angular gyrus specifically increases duringmeaningful phrasal composition. The anterior angular gyrus, on the other hand, guides morespecific compositionalprocessing evaluating phrasal plausibility. Overall, our results were stronger in the explicit task, pointing towards partly task-dependent involvement of the regions. Here we provide a separation between distinct nodes of the semantic network, whose functional contributions depend on the type of compositional process under analysis. For the first time, we show that the angular gyrus may be decomposable into two sub-regions during semantic composition.
Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease
Authors: Heinzel Sebastian , Aho Velma T. E. , Suenkel Ulrike , von Thaler Anna-Katharina , Schulte Claudia , Deuschle Christian , Paulin Lars , Hantunen Sari , Brockmann Kathrin , Eschweiler Gerhard W. , Maetzler Walter , Berg Daniela , Auvinen Petri , Scheperjans Filip
Published: December 2019

Objectives

Alterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.

Methods

Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.

Results

Among risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.

Interpretation

Several risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.
Physiological and genomic analysis of “CandidatusNitrosocosmicus agrestis”, an ammonia tolerant ammonia-oxidizing archaeon from vegetable soil
Authors: Liu Liangting , Liu Mengfan , Jiang Yiming , Lin Weitie , Luo Jianfei
Published: December 2019

The presences of ammonia tolerant ammonia-oxidizing archaea (AOA) in environments are always underestimated and their adaption to complex habitats has also rarely been reported. Here we present the physiological and genomic characteristics of an ammonia tolerant soil AOA strainCandidatusNitrosocosmicus agrestis. This strain was able to form aggregates and adhere on the surface of hydrophobic matrix. Ammonia-oxidizing activities were still observed at 200 mM NH4+(> 1500 μM of free ammonia) and 50 mM NO2-. Urea could be used as sole energy source but exogenous organics had no significant effect on the ammonia oxidation. Besides the genes involving in ammonia oxidation, carbon fixation and urea hydrolysis, the genome also encodes a full set of genes (GTs, GHs, CEs, MOP, LPSE, etc) that responsible for polysaccharide metabolism and secretion, suggesting the potential production of extracellular polymeric substances (EPS). Moreover, a pathway connecting urea cycle, polyamines synthesis and excretion was identified in the genome, which indicates the NH4+in cytoplasm could potentially be converted into polyamines and excreted out of cell, and then contributes to the high ammonia tolerance. Genes encoding the cytoplasmic carbonic anhydrase and putative polyamine exporter are unique inCa. Nitrosocosmicus agrestis or the genusCa. Nitrosocosmicus, suggesting the prevalence of ammonia tolerance in this clade. The proposed mechanism of ammonia tolerance via polyamines synthesis and export was verified by using transcriptional gene regulation and polyamines determination.

IMPORTANCE

AOA are ubiquitous in different environments and play a major role in nitrification. Though AOA have higher affinities for ammonia, their maximum specific cell activity and ammonia tolerance are usually much lower than AOB, resulting in low contribution to the global ammonia oxidation and N2O production. However, in some agricultural soils, the AOA activity would not be suppressed by the fertilization with high concentration of ammonium nitrogen, suggesting the presence of some ammonia tolerant species. This study provides some physiological and genomic characteristics for an ammonia tolerant soil AOA strainCa. Nitrosocosmicus agrestis and proposes some mechanisms of this AOA adapting to a variety of environments and tolerating to high ammonia. Ammonia tolerance of AOA was always underestimated in many previous studies, physiological and genomic analyses of this AOA clade are benefit to uncover the role of AOA playing in global environmental patterns.
Novel target identification using single cell sequencing and electrophysiology of cardiac sympathetic neurons in disease
Authors: Davis Harvey , Herring Neil , Paterson David J
Published: December 2019

The activity of cardiac sympathetic nerves from the stellate ganglia is increased in many cardiovascular diseases contributing to the pathophysiology, however the mechanisms underlying this are unknown. Moreover, clinical studies show their surgical removal is an effective treatment, despite the biophysical properties of these neurons being largely unstudied. Here we demonstrate that stellate ganglia neurons from prehypertensive spontaneously hypertensive rats are hyperactive and describe in detail their electrophysiological phenotype guided by single cell RNA-sequencing, molecular biology and perforated patch-clamp to uncover the underlying mechanism. The expression of key transcripts was confirmed in human stellate ganglia. We further demonstrate the contribution of a plethora of ion channels to stellate ganglia neuronal firing, and show that hyperexcitability was curbed by M-current activators, non-selective sodium current blockers or inhibition of Nav1.1-1.3, Nav1.6 or INaP. These findings have implications for target discovery to reduce cardiac sympathetic activity without resorting to surgery.
Human NMD ensues independently of stable ribosome stalling
Authors: Karousis Evangelos D. , Gurzeler Lukas-Adrian , Annibaldis Giuditta , Dreos René , Mühlemann Oliver
Published: December 2019

Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA degradation pathway that is important for the elimination of faulty and the regulation of normal mRNAs. The molecular details of the early steps in NMD are not fully understood but previous work suggests that NMD activation occurs as a consequence of ribosome stalling at the termination codon (TC). To test this hypothesis, we established anin vitrotranslation-coupled toeprinting assay based on lysates from human cells that allows monitoring of ribosome occupancy at the TC of reporter mRNAs. In contrast to the prevailing NMD model, ourin vitrosystem revealed similar ribosomal occupancy at the stop codons of NMD-sensitive and NMD-insensitive reporter mRNAs. Moreover, ribosome profiling revealed a similar density of ribosomes at the TC of endogenous NMD-sensitive and NMD-insensitive mRNAsin vivo. Together, these data show that NMD activation is not accompanied by stable stalling of ribosomes at TCs.
In VitroPlatform Establishes Antigen-Specific CD8+T Cell Cytotoxicity to Encapsulated Cells via Indirect Antigen Recognition
Authors: Li Ying , Frei Anthony W. , Yang Ethan Y. , Labrada-Miravet Irayme , Sun Chuqiao , Rong Yanan , Samojlik Magdalena M. , Bayer Allison L. , Stabler Cherie L.
Published: December 2019

Cell replacement therapy has the potential to cure diseases caused by the absence or malfunction of specialized cells. A substantial impediment to the success of any non-autologous cellular transplant is the need for systemic immunosuppressive drugs to prevent host-mediated rejection of the foreign cells. Cellular encapsulation, i.e., the entrapment of cells within stable polymeric hydrogels, has been clinically explored to prevent host immune recognition and attack, but the efficacy of these encapsulated grafts is poor. While several studies have explored improvements in innate immune acceptance of these encapsulated cells, little attention has been paid to the roles of adaptive immune responses, specifically graft-targeting T cell activation, in graft destabilization. Herein, we established an efficient, single-antigenin vitroplatform capable of delineating direct and indirect host T cell recognition to microencapsulated cellular grafts and evaluating their consequential impacts. Using alginate as the model hydrogel, encapsulated membrane-bound ovalbumin (mOVA) stimulator cells were incubated with antigen-specific OTI lymphocytes and subsequent OVA-specific CD8+T cell activation and effector function were quantified. We established that alginate microencapsulation abrogates direct T cell activation by interrupting donor-host interaction; however, indirect T cell activation mediated by host antigen presenting cells (APCs) primed with shed donor antigens still occurs. These activated T cells imparted cytotoxicity on the encapsulated cells, likely via diffusion of cytotoxic solutes. Overall, this platform delivers unique mechanistic insight into the impacts of hydrogel encapsulation on host adaptive immune responses, as well as a tool for the efficient immune screening on new encapsulation methods and/or synergistic immunomodulatory agents.
Efficient coding of natural scene statistics predicts discrimination thresholds for grayscale textures
Authors: Teşileanu Tiberiu , Conte Mary M. , Briguglio John J. , Hermundstad Ann M. , Victor Jonathan D. , Balasubramanian Vijay
Published: December 2019

Previously, in [1], we showed that when sampling is limiting, the efficient coding principle leads to a “variance is salience” hypothesis, and that this hypothesis accounts for visual sensitivity to binary image statistics. Here, using extensive new psychophysical data and image analysis, we show that this hypothesis accounts for visual sensitivity to a large set of grayscale image statistics at a striking level of detail, and also identify the limits of the prediction. We define a 66-dimensional space of local grayscale light-intensity correlations, and measure the relevance of each direction to natural scenes. The “variance is salience” hypothesis predicts that two-point correlations are most salient, and predicts their relative salience. We tested these predictions in a texture-segregation task using un-natural, synthetic textures. As predicted, correlations beyond second order are not salient, and predicted thresholds for over 300 second-order correlations match psychophysical thresholds closely (median fractional error < 0.13).
Modeling uniquely human gene regulatory function in humanized mice
Authors: Dutrow Emily V. , Emera Deena , Yim Kristina , Uebbing Severin , Kocher Acadia A. , Krenzer Martina , Nottoli Timothy , Burkhardt Daniel B. , Krishnaswamy Smita , Louvi Angeliki , Noonan James P.
Published: December 2019

The evolution of uniquely human traits likely entailed changes in developmental gene regulation. Human Accelerated Regions (HARs), which include transcriptional enhancers harboring a significant excess of human-specific sequence changes, are leading candidates for driving gene regulatory modifications in human development. However, insight into whether HARs alter the level, distribution and timing of endogenous gene expression remains limited. We examined the role of the HARHACNS1(HAR2) in human evolution by interrogating its molecular functions in a humanized mouse model. We find thatHACNS1maintains its human-specific enhancer activity in humanized mice and that it modifies expression ofGbx2, which encodes a homeobox transcription factor, during limb development. Using single-cell RNA-sequencing, we demonstrate thatGbx2is upregulated in the chondrogenic mesenchyme of humanized limbs, supporting thatHACNS1alters gene expression in cell types involved in skeletal patterning. Our findings illustrate that humanized mouse models provide mechanistic insight into how HARs modified gene expression in human evolution.
Honest signalling of trustworthiness
Authors: Roberts Gilbert
Published: December 2019

Trust can transform conflicting interests into cooperation. But how can individuals know when to trust others? Here, I develop the theory that reputation building may signal cooperative intent, or ‘trustworthiness’. I model a simple representation of this theory in which individuals (1) optionally invest in a reputation by performing costly helpful behaviour (‘signalling’); (2) optionally use others’ reputations when choosing a partner; and (3) optionally cooperate with that partner. In evolutionary simulations, high levels of reputation building; of choosing partners based on reputation; and of cooperation within partnerships emerged. Costly helping behaviour evolved into an honest signal of trustworthiness when it was adaptive for cooperators, relative to defectors, to invest in the long-term benefits of a reputation for helping. I show using game theory that this occurs when cooperators gain larger marginal benefits from investing in signalling than do defectors. This happens without the usual costly signalling assumption that individuals are of two ‘types’ which differ in quality. Signalling of trustworthiness may help explain phenomena such as philanthropy, pro-sociality, collective action, punishment, and advertising in humans and may be particularly applicable to courtship in other animals.
Biofilm and Cell Adhesion Strength on Dental Implant Surfaces via the Laser Spallation Technique
Authors: Boyd J. D. , Miller C.S. , Grady M. E.
Published: December 2019

Objectives

The aim of this study is to quantify the adhesion strength differential between an oral bacterial biofilm and an osteoblast-like cell monolayer to a dental implant-simulant surface and develop a metric that quantifies the biocompatible efficacy of implant surfaces.

Methods

High-amplitude short-duration stress waves generated by laser pulse absorption are used to spall bacteria and cells from titanium substrates. By carefully controlling laser fluence and calibration of laser fluence with applied stress, the adhesion difference between dental carryStreptococcus mutansbiofilms and MG 63 osteoblast-like cell monolayers on smooth and rough titanium substrates is obtained. The Adhesion Index consists of a ratio of cell adhesion strength to biofilm adhesion strength obtaining a nondimensionalized parameter for biocompatibility assessments.

Results

Adhesion strength of 145±42 MPa is measured for MG 63 on smooth titanium, which increases to 288±24 MPa on roughened titanium. Adhesion strength forS. mutanson smooth titanium is 315±9 MPa and remained relatively constant at 332±9 MPa on roughened titanium. The Adhesion Index for smooth titanium is 0.46±0.12 which increased to 0.87±0.05 on roughened titanium.

Significance

The laser spallation technique provides a platform to examine the tradeoffs of adhesion modulators on both biofilm and cell adhesion. This tradeoff is characterized by the Adhesion Index, which is proposed to aid biocompatibility screening and could result in improved implantation outcomes. The Adhesion Index is implemented to determine surface factors that promote favorable adhesion of cells greater than biofilms. Here, an Adhesion Index >> 1 suggests favorable biocompatibility.

Graphical Abstract

Highlights

Biofilm and cell monolayer adhesion are measured via the laser spallation technique

Smooth and roughened dental implant-mimicking titanium surfaces are investigated

Surface roughness increases cell adhesion but does not alter the adhesion of biofilms

An Adhesion Index is developed to directly quantify the adhesive competition between bacteria and cells on an implant surface
The transcriptional legacy of developmental stochasticity
Authors: Ballouz Sara , Pena Maria T. , Knight Frank M. , Adams Linda B. , Gillis Jesse A.
Published: December 2019

Genetic variation, epigenetic regulation and major environmental stimuli are key contributors to phenotypic variation, but the influence of minor perturbations or “noise” has been difficult to assess in mammals. In this work, we uncover one major axis of random variation with a large and permanent influence: developmental stochasticity. By assaying the transcriptome of wild monozygotic quadruplets of the nine-banded armadillo, we find that persistent changes occur early in development, and these give rise to clear transcriptional signatures which uniquely characterize individuals relative to siblings. Comparing these results to human twins, we find the transcriptional signatures which define individuals exhibit conserved co-expression, suggesting a substantial fraction of phenotypic and disease discordance within mammals arises from developmental stochasticity.

One sentence summary

Longitudinal gene expression in identical armadillo quadruplets reveals a major role for developmental stochasticity.
Expansion and re-classification of the extracytoplasmic function (ECF) σ factor family
Authors: Casas-Pastor Delia , Müller Raphael Rene , Becker Anke , Buttner Mark , Gross Carol , Mascher Thorsten , Goesmann Alexander , Fritz Georg
Published: December 2019

Extracytoplasmic function σ factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As result, we identified ∼10 ECFs per bacterial genome on average and classified them into 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands the number of unique ECF sequences ∼50-fold relative to previous classification efforts, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences, enables the application ofin silicotools for the prediction of important functional residues, and serves as a powerful hypothesis-generator to guide future research in the field.
Localization of immunoreactive, dystonia-associated protein torsinA near the Golgi apparatus of cultured rodent astrocytes
Authors: Iwabuchi Sadahiro , Kawano Hiroyuki , Harata N. Charles
Published: December 2019

An in-frame deletion of a single glutamic acid codon in theTOR1Agene causes the neurological disorder DYT1 dystonia, but the cellular pathophysiology of this disorder remains elusive. A current model postulates that the wild-type (WT) torsinA protein is mainly localized to the endoplasmic reticulum (ER), but that the mutant form (ΔE-torsinA) is diverted to the nuclear envelope and cytoplasmic inclusion bodies. This mis-localization has been observed by overexpressing the proteins in neuronal and non-neuronal cells. However, it is not clear whether this model is valid for the astrocytic glial cells that support and modify neuronal functions. Here we report, using rodent astrocytes in primary culture, that the overexpressed torsinA proteins were distributed as predicted by the mis-localization model. We also found by immunocytochemistry that the cultured astrocytes express torsinA endogenously. Most of the signals from endogenous protein, whether the WT or ΔE form, were localized near acis-Golgi marker GM130. Such localization of endogenous proteins was found in glial cells from several sources: the hippocampus of WT rats, the hippocampus and striatum of WT mice, and the hippocampus and striatum of ΔE-torsinA knock-in mice, a model of DYT1 dystonia. These results show that the mis-localization model is applicable to overexpressed torsinA proteins, but not applicable to those expressed at endogenous levels, at least in cultured rodent astrocytes. These discrepancies in the distribution of overexpressed versus endogenous torsinA proteins highlight the potential need for caution in interpreting the results of overexpression studies.
Flapping at Resonance: Measuring the Frequency Response of the Hymenoptera Thorax
Authors: Jankauski Mark A.
Published: December 2019

Insects with asynchronous flight muscles are believed to flap at the fundamental frequency of their thorax or thorax-wing system. Flapping in this manner leverages the natural elasticity of the thorax to reduce the energetic requirements of flight. However, to the best of our knowledge, the fundamental frequency of the insect thorax has not been measured via vibration testing. Here, we measure the linear frequency response function (FRF) of several Hymenoptera (Apis mellifera, Polistes dominula, Bombus huntii) thoraxes about their equilibrium states in order to determine their fundamental frequencies. FRFs relate the input force to output acceleration at the insect tergum and are acquired via a mechanical vibration shaker assembly. When compressed 50μm, thorax fundamental frequencies in all specimens approximately 50-150% higher than reported wingbeat frequencies. We suspect that the measured fundamental frequencies are higher in the experiment than during flight due to experimental boundary conditions that stiffen the thorax. Thus, our results corroborate the idea that some insects flap at the fundamental frequency of their thorax. Next, we compress the thorax between 100 - 300 μm in 50 μm intervals to assess the sensitivity of the fundamental frequency to geometric modifications. For all insects considered, the thorax fundamental frequency increased nearly monotonically with respect to level of compression. This implies that the thorax behaves a nonlinear hardening spring, which we confirmed via static force-displacement testing. Hardening behavior may provide a simple mechanism for the insect to adjust wingbeat frequency, and implies the thorax may behave as a nonlinear Duffing oscillator excited at large amplitude. The Duffing oscillator exhibits amplitude-dependent resonance and may serve as a useful model to increase the flapping frequency bandwidth of small resonant-type flapping wing micro air vehicles.
GtcA is required for LTA glycosylation inListeria monocytogenesserovar 1/2a andBacillus subtilis
Authors: Rismondo Jeanine , Haddad Talal F. M. , Shen Yang , Loessner Martin J. , Gründling Angelika
Published: December 2019

The cell wall polymers wall teichoic acid (WTA) and lipoteichoic acid (LTA) are often modified with glycosyl and D-alanine residues. Recent studies have shown that a three-component glycosylation system is used for the modification of LTA in several Gram-positive bacteria includingBacillus subtilisandListeria monocytogenes. In theL. monocytogenes1/2a strain 10403S, the cytoplasmic glycosyltransferase GtlA is thought to use UDP-galactose to produce the C55-P-galactose lipid intermediate, which is transported across the membrane by an unknown flippase. Next, the galactose residue is transferred onto the LTA backbone on the outside of the cell by the glycosyltransferase GtlB. Here we show that GtcA is necessary for the glycosylation of LTA inL. monocytogenes10403S andB. subtilis168 and we hypothesize that these proteins act as C55-P-sugar flippases. With this we revealed that GtcA is involved in the glycosylation of both teichoic acid polymers inL. monocytogenes10403S, namely WTA with N-acetylglucosamine and LTA with galactose residues. These findings indicate that theL. monocytogenesGtcA protein can act on different C55-P-sugar intermediates. Further characterization of GtcA inL. monocytogenesled to the identification of residues essential for its overall function as well as residues, which predominately impact WTA or LTA glycosylation.

GRAPHICAL ABSTRACT
Direct antiviral activity of interferon stimulated genes is responsible for resistance to paramyxoviruses in ISG15-deficient cells
Authors: Holthaus David , Vasou Andri , Bamford Connor G. G. , Andrejeva Jelena , Paulus Christina , Randall Richard E. , McLauchlan John , Hughes David J.
Published: December 2019

Interferons (IFNs), produced during viral infections, induce the expression of hundreds of IFN- stimulated genes (ISGs). Some ISGs have specific antiviral activity while others regulate the cellular response. Besides functioning as an antiviral effector, IFN-stimulated gene 15 (ISG15) is a negative regulator of IFN signalling and inherited ISG15-deficiency leads to autoinflammatory interferonopathies where individuals exhibit elevated ISG expression in the absence of pathogenic infection. We have recapitulated these effects in cultured human A549-ISG15-/-cells and (using A549-UBA7-/-cells) confirmed that posttranslational modification by ISG15 (ISGylation) is not required for regulation of the type-I IFN response. ISG15-deficient cells pre-treated with IFN-α were resistant to paramyxovirus infection. We also showed that IFN-α treatment of ISG15-deficient cells led to significant inhibition of global protein synthesis leading us to ask whether resistance was due to the direct antiviral activity of ISGs or whether cells were non-permissive due to translation defects. We took advantage of the knowledge that IFN-induced protein with tetratricopeptide repeats 1 (IFIT1) is the principal antiviral ISG for parainfluenza virus 5 (PIV5). Knockdown of IFIT1 restored PIV5 infection in IFN-α-pre-treated ISG15-deficient cells, confirming that resistance was due to the direct antiviral activity of the IFN response. However, resistance could be induced if cells were pre-treated with IFN-α for longer times, presumably due to inhibition of protein synthesis. These data show that the cause of virus resistance is two-fold; ISG15-deficiency leads to the ‘early’ over-expression of specific antiviral ISGs, but the later response is dominated by an unanticipated, ISG15- dependent, loss of translational control.

Key points

Cell culture model of ISG15-deficiency replicate findings in ISG15-/-patient cells

Cause of resistance in ISG15-/-cells differs depending on duration of IFN treatment

ISG15-/-patients without serious viral disease don’t prove ISGylation is unimportant
An improved ATP FRET sensor for yeast shows heterogeneity during nutrient transitions
Authors: Botman Dennis , van Heerden Johan H. , Teusink Bas
Published: December 2019

Adenosine 5-triphosphate (ATP) is the main free energy carrier in metabolism. In budding yeast, shifts to glucose-rich conditions cause dynamic changes in ATP levels, but it is unclear how heterogeneous these dynamics are at the single-cell level. Furthermore, pH also changes and affects readout of fluorescence-based biosensors for single-cell measurements. To measure ATP changes reliably in single yeast cells, we developed yAT1.03, an adapted version of the AT1.03 ATP biosensor, that is pH-insensitive. We show that pregrowth conditions largely affect ATP dynamics during transitions. Moreover, single-cell analyses showed a large variety in ATP responses, which implies large differences of glycolytic startup between individual cells. We found three clusters of dynamic responses, and show that a small subpopulation of wild type cells reached an imbalanced state during glycolytic startup, characterised by low ATP levels. These results confirm the need for new tools to study dynamic responses of individual cells in dynamic environments.
Viola unica (Violaceae L.), a very rare, high elevation, single-site new species endemic to the northern semi-desert Altiplano of Chile
Authors: Watson John Michael , Flores Ana Rosa
Published: December 2019

While examining the Viola collection at the herbarium (SGO) of the Museo Nacional de Historia Natural (MNHN), Santiago, we encountered a folder with a single unidentified specimen consisting of a solitary rosette. It had been found in northern Chile near the border with Bolivia, where considerable mining activity takes place. The plant appeared to differ from all others related to it as known to ourselves, and on investigation it did indeed prove to be undescribed. It is presented herein, together with a detailed analysis and preliminary partial revision of related taxa, including a key.
Aurora B and C kinases regulate prophase exit and chromosome segregation during spermatogenesis
Authors: Wellard Stephen R. , Schindler Karen , Jordan Philip
Published: December 2019

Precise control of chromosome dynamics during meiosis is critical for fertility. A gametocyte undergoing meiosis coordinates formation of the synaptonemal complex (SC) to promote efficient homologous chromosome recombination. Subsequent disassembly of the SC is required prior to meiotic divisions to ensure accurate segregation of chromosomes. We examined the requirements of the mammalian Aurora kinases (AURKA, B, and C) during SC disassembly and chromosome segregation using a combination of chemical inhibition and gene deletion approaches. We find that both mouse and human spermatocytes fail to disassemble SC lateral elements when AURKB and AURKC are inhibited. Interestingly, both Aurkb conditional knockout and Aurkc knockout spermatocytes successfully progress through meiosis and mice are fertile. In contrast, Aurkb, Aurkc double knockout spermatocytes failed to coordinate disassembly of SC lateral elements with chromosome segregation, resulting in delayed meiotic progression, spindle assembly checkpoint failure, chromosome missegregation, and abnormal spermatids. Collectively, our data demonstrates that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis.

Chemical inhibition and gene deletion approaches show that Aurora B and Aurora C have overlapping functions that ensure timely disassembly of lateral element components of the synaptonemal complex in mouse and human spermatocytes and ensure accurate chromosome segregation during meiosis.
Interpreting Wide-Band Neural Activity Using Convolutional Neural Networks
Authors: Frey Markus , Tanni Sander , Perrodin Catherine , O’Leary Alice , Nau Matthias , Kelly Jack , Banino Andrea , Bendor Daniel , Doeller Christian F. , Barry Caswell
Published: December 2019

Abstract

Rapid progress in technologies such as calcium imaging and electrophysiology has seen a dramatic increase in the size and extent of neural recordings. Even so, interpretation of this data often depends on manual operations and requires considerable knowledge about the nature of the representation. Decoding provides a means to infer the information content of such recordings but typically requires highly processed data and prior knowledge of the encoding scheme. Here, we developed a deep-learning-framework able to decode sensory and behavioural variables directly from wide-band neural data. The network requires little user input and generalizes across stimuli, behaviours, brain regions, and recording techniques. Once trained, it can be analysed to determine elements of the neural code that are informative about a given variable. We validated this approach using data from rodent auditory cortex and hippocampus, identifying a novel representation of head direction encoded by putative CA1 interneurons.