bluuebunny/crossref_metadata_2025 huggingface dataset:
Density Effects at a Concordant Bed Natural River Confluence
Authors: Horna‐Munoz Daniel , Constantinescu George , Rhoads Bruce , Lewis Quinn , Sukhodolov Alexander
Published: February 2020

Confluences are locations of complex hydrodynamic conditions within river systems. The effects on hydrodynamics and mixing of temperature‐induced density differences between incoming flows are investigated at a small‐size, concordant bed confluence. To evaluate density effects, results of eddy‐resolving simulations for a densimetric Froude number Fr = 4.9 (weak‐density‐effects cases) and Fr = 1.6 (strong‐density‐effects cases) are compared to results of simulations in which the densities of the incoming flows do not differ (no‐density‐effects cases). Flow patterns predicted for both weak‐ and strong‐density‐effects cases show that secondary flow develops with increasing distance from the confluence apex. The pattern of secondary flow is characterized by denser fluid on one side of the confluence moving near the bed toward the side of the downstream channel corresponding to the less dense fluid and the less dense fluid moving near the free surface in the opposite direction. This pattern of fluid motion is similar to a spatially evolving lock‐exchange cross flow. In the strong‐density‐effects simulations, a cross‐stream cell of secondary flow develops at the density interface between the flows, similar to interfacial billows generated in classical lock‐exchange flows. Density effects increase global mixing with respect to corresponding no‐density‐effects cases regardless of whether the high‐momentum stream contains the higher‐density fluid or the lower‐density fluid. When density effects are weak, the lock‐exchange mechanism either reinforces the pattern of mixing associated with secondary flow induced by inertial forces, particularly helical motion, or opposes this pattern of mixing, depending on which tributary contains the denser fluid. When density effects are strong, flow from the upstream channel with the denser fluid moves under the flow from the upstream channel with the less dense fluid.
Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin
Authors: Abdallah Chadi G. , Averill Lynnette A. , Gueorguieva Ralitza , Goktas Selin , Purohit Prerana , Ranganathan Mohini , Sherif Mohamed , Ahn Kyung-Heup , D’Souza Deepak Cyril , Formica Richard , Southwick Steven M. , Duman Ronald S. , Sanacora Gerard , Krystal John H.
Published: February 2020

Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized to pretreatment with oral rapamycin (6 mg) or placebo 2 h prior to the intravenous administration of ketamine 0.5 mg/kg in a double-blind cross-over design with treatment days separated by at least 2 weeks. Depression severity was assessed using Montgomery–Åsberg Depression Rating Scale (MADRS). Rapamycin pretreatment did not alter the antidepressant effects of ketamine at the 24-h timepoint. Over the subsequent 2-weeks, we found a significant treatment by time interaction (F(8,245) = 2.02, p = 0.04), suggesting a prolongation of the antidepressant effects of ketamine by rapamycin. Two weeks following ketamine administration, we found higher response (41%) and remission rates (29%) following rapamycin + ketamine compared to placebo + ketamine (13%, p = 0.04, and 7%, p = 0.003, respectively). In summary, single dose rapamycin pretreatment failed to block the antidepressant effects of ketamine, but it prolonged ketamine’s antidepressant effects. This observation raises questions about the role of systemic vs. local blockade of mTORC1 in the antidepressant effects of ketamine, provides preliminary evidence that rapamycin may extend the benefits of ketamine, and thereby potentially sheds light on mechanisms that contribute to depression relapse after ketamine administration.
Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease
Authors: Hollander Jonathan A. , Cory-Slechta Deborah A. , Jacka Felice N. , Szabo Steven T. , Guilarte Tomás R. , Bilbo Staci D. , Mattingly Carolyn J. , Moy Sheryl S. , Haroon Ebrahim , Hornig Mady , Levin Edward D. , Pletnikov Mikhail V. , Zehr Julia L. , McAllister Kimberly A. , Dzierlenga Anika L. , Garton Amanda E. , Lawler Cindy P. , Ladd-Acosta Christine
Published: February 2020

The etiologic pathways leading to neuropsychiatric diseases remain poorly defined. As genomic technologies have advanced over the past several decades, considerable progress has been made linking neuropsychiatric disorders to genetic underpinnings. Interest and consideration of nongenetic risk factors (e.g., lead exposure and schizophrenia) have, in contrast, lagged behind heritable frameworks of explanation. Thus, the association of neuropsychiatric illness to environmental chemical exposure, and their potential interactions with genetic susceptibility, are largely unexplored. In this review, we describe emerging approaches for considering the impact of chemical risk factors acting alone and in concert with genetic risk, and point to the potential role of epigenetics in mediating exposure effects on transcription of genes implicated in mental disorders. We highlight recent examples of research in nongenetic risk factors in psychiatric disorders that point to potential shared biological mechanisms—synaptic dysfunction, immune alterations, and gut–brain interactions. We outline new tools and resources that can be harnessed for the study of environmental factors in psychiatric disorders. These tools, combined with emerging experimental evidence, suggest that there is a need to broadly incorporate environmental exposures in psychiatric research, with the ultimate goal of identifying modifiable risk factors and informing new treatment strategies for neuropsychiatric disease.
Population genomics and evolution of a fungal pathogen after releasing exotic strains to control insect pests for 20 years
Authors: Mei Lijuan , Chen Mingjun , Shang Yanfang , Tang Guirong , Tao Ye , Zeng Liang , Huang Bo , Li Zengzhi , Zhan Shuai , Wang Chengshu
Published: February 2020

Entomopathogenic fungi are one of the key regulators of insect populations in nature. Some species such as Beauveria bassiana with a wide host range have been developed as promising alternatives to chemical insecticides for the biocontrol of insect pests. However, the long-term persistence of the released strains, the effect on non-target hosts and local fungal populations remains elusive, but they are considerable concerns with respect to environmental safety. Here we report the temporal features of the Beauveria population genomics and evolution over 20 years after releasing exotic strains to control pine caterpillar pests. We found that the isolates within the biocontrol site were mostly of clonal origins. The released strains could persist in the environment for a long time but with low recovery rates. Similar to the reoccurrence of host jumping by local isolates, the infection of non-target insects by the released strains was evident to endemically occur in association with host seasonality. No obvious dilution effect on local population structure was evident by the releases. However, the population was largely replaced by genetically divergent isolates once per decade but evolved with a pattern of balancing selection and towards expansion through adaptation, non-random outcrossing and isolate migration. This study not only unveils the real-time features of entomopathogenic fungal population genomics and evolution but also provides added values to alleviate the concerns of environmental safety regarding the biocontrol application of mycoinsecticides.
Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis
Authors: Schwaderer Juliane , Phan Truong San , Glöckner Astrid , Delp Johannes , Leist Marcel , Brunner Thomas , Delgado M. Eugenia
Published: February 2020

Liver receptor homolog-1 (LRH-1, Nr5a2) is an orphan nuclear receptor mainly expressed in tissues of endodermal origin, where its physiological role has been extensively studied. LRH-1 has been implicated in liver cell differentiation and proliferation, as well as glucose, lipid, and bile acid metabolism. In addition, increasing evidence highlights its role in immunoregulatory processes via glucocorticoid synthesis in the intestinal epithelium. Although the direct function of LRH-1 in immune cells is fairly elucidated, a role of LRH-1 in the regulation of macrophage differentiation has been recently reported. In this study, we aimed to investigate the role of LRH-1 in the regulation of pro-inflammatory cytokine production in macrophages. Our data demonstrate that pharmacological inhibition, along with LRH-1 knockdown, significantly reduced the lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines in the macrophage line RAW 264.7 cells, as well as in primary murine macrophages. This inhibitory effect was found to be independent of defects of LRH-1-regulated cell proliferation or toxic effects of the LRH-1 inhibitors. In contrast, LRH-1 inhibition reduced the mitochondrial ATP production and metabolism of macrophages through downregulation of the LRH-1 targets glucokinase and glutminase-2, and thus impairing the LPS-induced macrophage activation. Interestingly, in vivo pharmacological inhibition of LRH-1 also resulted in reduced tumor necrosis factor (TNF) production and associated decreased liver damage in a macrophage- and TNF-dependent mouse model of hepatitis. Noteworthy, despite hepatocytes expressing high levels of LRH-1, pharmacological inhibition of LRH-1 per se did not cause any obvious liver damage. Therefore, this study proposes LRH-1 as an emerging therapeutic target in the treatment of inflammatory disorders, especially where macrophages and cytokines critically decide the extent of inflammation.
Molecular trapping in two-dimensional chiral organic Kagomé nanoarchitectures composed of Baravelle spiral triangle enantiomers
Authors: Dong Meiqiu , Miao Xinrui , Brisse Romain , Deng Wenli , Jousselme Bruno , Silly Fabien
Published: February 2020

The supramolecular self-assembly of a push-pull dye is investigated using scanning tunneling microscopy (STM) at the liquid–solid interface. The molecule has an indandione head, a bithiophene backbone and a triphenylamine–bithiophene moiety functionalized with two carboxylic acid groups as a tail. The STM images show that the molecules adopt an “L” shape on the surface and form chiral Baravelle spiral triangular trimers at low solution concentrations. The assembly of these triangular chiral trimers on the graphite surface results in the formation of two types of chiral Kagomé nanoarchitectures. The Kagomé-α structure is composed of only one trimer enantiomer, whereas the Kagomé-β structure results from the arrangement of two trimer enantiomers in a 1:1 ratio. These Kagomé lattices are stabilized by intermolecular O-H···O hydrogen bonds between carboxylic acid groups. These observations reveal that the complex structure of the push-pull dye molecule leads to the formation of sophisticated two-dimensional chiral Kagomé nanoarchitectures. The subsequent deposition of coronene molecules leads to the disappearance of the Kagomé-β structure, whereas the Kagomé-α structure acts as the host template to trap the coronene molecules.
Adverse caregiving in infancy blunts neural processing of the mother
Authors: Opendak Maya , Theisen Emma , Blomkvist Anna , Hollis Kaitlin , Lind Teresa , Sarro Emma , Lundström Johan N. , Tottenham Nim , Dozier Mary , Wilson Donald A. , Sullivan Regina M.
Published: February 2020

The roots of psychopathology frequently take shape during infancy in the context of parent-infant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother. We show that during adversity, pup cortical LFP dynamic range decreased during nurturing maternal behaviors, but was minimally impacted by rough handling. During reunion, adversity-experiencing pups showed aberrant interactions with mother and blunted cortical LFP. Blocking pup stress hormone during either adversity or reunion restored typical behavior, LFP power, and cross-frequency coupling. This translational approach suggests adversity-rearing produces a stress-induced aberrant neurobehavioral processing of the mother, which can be used as an early biomarker of later-life pathology.
Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism
Authors: Loregger Anke , Raaben Matthijs , Nieuwenhuis Joppe , Tan Josephine M. E. , Jae Lucas T. , van den Hengel Lisa G. , Hendrix Sebastian , van den Berg Marlene , Scheij Saskia , Song Ji-Ying , Huijbers Ivo J. , Kroese Lona J. , Ottenhoff Roelof , van Weeghel Michel , van de Sluis Bart , Brummelkamp Thijn , Zelcer Noam
Published: February 2020

The sterol-regulatory element binding proteins (SREBP) are central transcriptional regulators of lipid metabolism. Using haploid genetic screens we identify the SREBPRegulating Gene (SPRING/C12ORF49) as a determinant of the SREBP pathway. SPRING is a glycosylated Golgi-resident membrane protein and its ablation in Hap1 cells, Hepa1-6 hepatoma cells, and primary murine hepatocytes reduces SREBP signaling. In mice, Spring deletion is embryonic lethal yet silencing of hepatic Spring expression also attenuates the SREBP response. Mechanistically, attenuated SREBP signaling in SPRINGKO cells results from reduced SREBP cleavage-activating protein (SCAP) and its mislocalization to the Golgi irrespective of the cellular sterol status. Consistent with limited functional SCAP in SPRINGKO cells, reintroducing SCAP restores SREBP-dependent signaling and function. Moreover, in line with the role of SREBP in tumor growth, a wide range of tumor cell lines display dependency on SPRING expression. In conclusion, we identify SPRING as a previously unrecognized modulator of SREBP signaling.
Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response
Authors: Yu Xiang , Dai Yanfeng , Zhao Yifan , Qi Shuhong , Liu Lei , Lu Lisen , Luo Qingming , Zhang Zhihong
Published: February 2020

Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of this technique is restricted by the paucity of suitable tumor-associated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (α-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, α-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8+ T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by α-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, α-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine.
Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance
Authors: Martens Rieke , Permanyer Marc , Werth Kathrin , Yu Kai , Braun Asolina , Halle Olga , Halle Stephan , Patzer Gwendolyn E. , Bošnjak Berislav , Kiefer Friedemann , Janssen Anika , Friedrichsen Michaela , Poetzsch Jenny , Kohli Karan , Lueder Yvonne , Gutierrez Jauregui Rodrigo , Eckert Nadine , Worbs Tim , Galla Melanie , Förster Reinhold
Published: February 2020

Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS). Arrested T cells subsequently migrate randomly on the sinus floor independent of both chemokines and integrins. However, chemokine receptors are imperative for guiding cells out of the SCS, and for their subsequent directional translocation towards the T cell zone. By contrast, integrins are dispensable for LN homing, yet still contribute by increasing the dwell time within the SCS and by potentially enhancing T cell sensing of chemokine gradients. Together, these findings provide fundamental insights into mechanisms that control homing of lymph-derived immune cells.
Elliptical Bloch skyrmion chiral twins in an antiskyrmion system
Authors: Jena Jagannath , Göbel Börge , Ma Tianping , Kumar Vivek , Saha Rana , Mertig Ingrid , Felser Claudia , Parkin Stuart S. P.
Published: February 2020

Skyrmions and antiskyrmions are distinct topological chiral spin textures that have been observed in various material systems depending on the symmetry of the crystal structure. Here we show, using Lorentz transmission electron microscopy, that arrays of skyrmions can be stabilized in a tetragonal inverse Heusler with D2d symmetry whose Dzyaloshinskii-Moriya interaction (DMI) otherwise supports antiskyrmions. These skyrmions can be distinguished from those previously found in several B20 systems which have only one chirality and are circular in shape. We find Bloch-type elliptical skyrmions with opposite chiralities whose major axis is oriented along two specific crystal directions: [010] and [100]. These structures are metastable over a wide temperature range and we show that they are stabilized by long-range dipole-dipole interactions. The possibility of forming two distinct chiral spin textures with opposite topological charges of ±1 in one material makes the family of D2d materials exceptional.
Stem rust resistance in wheat is suppressed by a subunit of the mediator complex
Authors: Hiebert Colin W. , Moscou Matthew J. , Hewitt Tim , Steuernagel Burkhard , Hernández-Pinzón Inma , Green Phon , Pujol Vincent , Zhang Peng , Rouse Matthew N. , Jin Yue , McIntosh Robert A. , Upadhyaya Narayana , Zhang Jianping , Bhavani Sridhar , Vrána Jan , Karafiátová Miroslava , Huang Li , Fetch Tom , Doležel Jaroslav , Wulff Brande B. H. , Lagudah Evans , Spielmeyer Wolfgang
Published: February 2020

Stem rust is an important disease of wheat that can be controlled using resistance genes. The geneSuSr-D1identified in cultivar ‘Canthatch’ suppresses stem rust resistance.SuSr-D1mutants are resistant to several races of stem rust that are virulent on wild-type plants. Here we identifySuSr-D1by sequencing flow-sorted chromosomes, mutagenesis, and map-based cloning. The gene encodes Med15, a subunit of the Mediator Complex, a conserved protein complex in eukaryotes that regulates expression of protein-coding genes. Nonsense mutations in Med15b.D result in expression of stem rust resistance. Time-course RNAseq analysis show a significant reduction or complete loss of differential gene expression at 24 h post inoculation inmed15b.Dmutants, suggesting that transcriptional reprogramming at this time point is not required for immunity to stem rust. Suppression is a common phenomenon and this study provides novel insight into suppression of rust resistance in wheat.
Vertical eddy iron fluxes support primary production in the open Southern Ocean
Authors: Uchida Takaya , Balwada Dhruv , P. Abernathey Ryan , A. McKinley Galen , K. Smith Shafer , Lévy Marina
Published: February 2020

The primary productivity of the Southern Ocean ecosystem is limited by iron availability. Away from benthic and aeolian sources, iron reaches phytoplankton primarily when iron-rich subsurface waters enter the euphotic zone. Here, eddy-resolving physical/biogeochemical simulations of a seasonally-forced, open-Southern-Ocean ecosystem reveal that mesoscale and submesoscale isopycnal stirring effects a cross-mixed-layer-base transport of iron that sustains primary productivity. The eddy-driven iron supply and consequently productivity increase with model resolution. We show the eddy flux can be represented by specific well-tuned eddy parametrizations. Since eddy mixing rates are sensitive to wind forcing and large-scale hydrographic changes, these findings suggest a new mechanism for modulating the Southern Ocean biological pump on climate timescales.
Publisher Correction: Misophonia is associated with altered brain activity in the auditory cortex and salience network
Authors: Schröder Arjan , van Wingen Guido , Eijsker Nadine , San Giorgi Renée , Vulink Nienke C. , Turbyne Collin , Denys Damiaan
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A 3D printing approach toward targeted intervention in telerehabilitation
Authors: Barak Ventura Roni , Rizzo Alessandro , Nov Oded , Porfiri Maurizio
Published: February 2020

Neuromuscular impairment requires adherence to a rehabilitation regimen for maximum recovery of motor function. Consumer-grade game controllers have emerged as a viable means to relay supervised physical therapy to patients’ homes, thereby increasing their accessibility to healthcare. These controllers allow patients to perform exercise frequently and improve their rehabilitation outcomes. However, the non-universal design of game controllers targets healthy people and does not always accommodate people with disability. Consequently, many patients experience considerable difficulty assuming certain hand postures and performing the prescribed exercise correctly. Here, we explore the feasibility of improving rehabilitation outcomes through a 3D printing approach that enhances off-the-shelf game controllers in home therapy. Specifically, a custom attachment was 3D printed for a commercial haptic device that mediates fine motor rehabilitation. In an experimental study, 25 healthy subjects performed a navigation task, with the retrofit attachment and without it, while simulating disability of the upper limb. When using the attachment, subjects extended their wrist range of motion, yet maintained their level of compensation. The subjects also showed higher motivation to repeat the exercise with the enhanced device. The results bring forward evidence for the potential of this approach in transforming game controllers toward targeted interventions in home therapy.
Enrichment and characterisation of ethanol chain elongating communities from natural and engineered environments
Authors: Candry Pieter , Huang Shengle , Carvajal-Arroyo José Maria , Rabaey Korneel , Ganigue Ramon
Published: February 2020

Chain elongation is a microbial process in which an electron donor, such as ethanol, is used to elongate short chain carboxylic acids, such as acetic acid, to medium chain carboxylic acids. This metabolism has been extensively investigated, but the spread and differentiation of chain elongators in the environment remains unexplored. Here, chain elongating communities were enriched from several inocula (3 anaerobic digesters, 2 animal faeces and 1 caproic acid producing environment) using ethanol and acetic acid as substrates at pH 7 and 5.5. This approach showed that (i) the inoculum’s origin determines the pH where native chain elongators can grow; (ii) pH affects caproic acid production, with average caproic acid concentrations of 6.4 ± 1.6  g·L−1 at pH 7, versus 2.3 ± 1.8  g·L−1 at pH 5.5; however (iii) pH does not affect growth rates significantly; (iv) all communities contained a close relative of the known chain elongator Clostridium kluyveri; and (v) low pH selects for communities more enriched in this Clostridium kluyveri-relative (57.6 ± 23.2% at pH 7, 96.9 ± 1.2% at pH 5.5). These observations show that ethanol-consuming chain elongators can be found in several natural and engineered environments, but are not the same everywhere, emphasising the need for careful inoculum selection during process development.
T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management
Authors: Ponchel Frederique , Burska Agata N. , Hunt Laura , Gul Hanna , Rabin Thibault , Parmar Rekha , Buch Maya H. , Conaghan Philip G. , Emery Paul
Published: February 2020

The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p < 0.0001). In evolving IA patients, 219/294 developed RA; the risk-score included naïve and/or Treg and predicted progression (p < 0.0001). In 120 untreated RA patients, the risk-score for predicting treatment-induced remission using naïve T-cells had an odds ratio of 15.4 (p < 0.0001). In RA patients in treatment-induced remission, a score using naïve T-cells predicted disease flare (p < 0.0001). Evaluating the risk of progression using naïve CD4+ T-cells was predictive of progression along the whole IA-continuum. This should allow identification of individuals at high-risk of progression, permitting targeted therapy for improved outcomes.
Artificial shaking signals in honey bee colonies elicit natural responses
Authors: Koenig Phoebe A. , Smith Michael L. , Horowitz Logan H. , Palmer Daniel M. , Petersen Kirstin H.
Published: February 2020

Honey bee signals are primarily studied through natural observation combined with manipulations of the colony or environment, not direct manipulation of the signal stimulus or receivers. Consequently, we know little about which signal aspects are necessary to reproduce behavioral responses. Here, we focus on the shaking signal, wherein a worker grabs onto another bee and vibrates. All castes receive shaking signals, but individual responses depend on context, and the signal may be multi-modal (mechanical, odor, sound, etc.). We designed a tool to mimic the shaking signal. We tested whether a purely mechanical stimulus elicited the same behavioral response as a natural shaking signal, teasing apart the effects of signal and receiver characteristics. We found that both workers and drones increased their movement after being artificially shaken, and that shaken drones were more likely to engage in feeding and grooming than a sham control. These behavioral changes support the idea that the shaking signal serves to generally increase worker activity, but also serves to activate male reproductives (drones). With this tool, we show that vibration itself is responsible for eliciting much of the shaking signal’s behavioral response, in one of the few examples of direct playback in social insects.
Antibody transcytosis across brain endothelial-like cells occurs nonspecifically and independent of FcRn
Authors: Ruano-Salguero John S. , Lee Kelvin H.
Published: February 2020

The blood-brain barrier (BBB) hinders the brain delivery of therapeutic immunoglobulin γ (IgG) antibodies. Evidence suggests that IgG-specific processing occurs within the endothelium of the BBB, but any influence on transcytosis remains unclear. Here, involvement of the neonatal Fc receptor (FcRn), which mediates IgG recycling and transcytosis in peripheral endothelium, was investigated by evaluating the transcytosis of IgGs with native or reduced FcRn engagement across human induced pluripotent stem cell-derived brain endothelial-like cells. Despite differential trafficking, the permeability of all tested IgGs were comparable and remained constant irrespective of concentration or competition with excess IgG, suggesting IgG transcytosis occurs nonspecifically and originates from fluid-phase endocytosis. Comparison with the receptor-enhanced permeability of transferrin indicates that the phenomena observed for IgG is ubiquitous for most macromolecules. However, increased permeability was observed for macromolecules with biophysical properties known to engage alternative endocytosis mechanisms, highlighting the importance of biophysical characterizations in assessing transcytosis mechanisms.
No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus
Authors: Kieninger-Gräfitsch A. , Vogt S. , Ribi C. , Dubler D. , Chizzolini C. , Huynh-Do U. , Osthoff M. , Trendelenburg M.
Published: February 2020

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.
Genetic assignment of illegally trafficked neotropical primates and implications for reintroduction programs
Authors: Oklander Luciana Inés , Caputo Mariela , Solari Agustín , Corach Daniel
Published: February 2020

The black and gold howler monkey (Alouatta caraya) is a neotropical primate threatened by habitat loss and capture for illegal trade in Argentina. Using multilocus microsatellite genotypes from 178 A. carayaindividuals sampled from 15 localities in Argentina, we built a genotype reference database (GRDB). Bayesian assignment methods applied to the GRDB allowed us to correctly re-assign 73% of individuals to their true location of origin and 93.3% to their cluster of origin. We used the GRDB to assign 22 confiscated individuals (17 of which were reintroduced), and 3 corpses to both localities and clusters of origin. We assigned with a probability >70% the locality of origin of 14 individuals and the cluster of origin of 21. We found that most of the confiscated individuals were assigned to one cluster (F-Ch-C) and two localities included in the GRDB, suggesting that traffickedA. carayaprimarily originated in this area. Our results reveal that only 4 of 17 reintroduced individuals were released in sites corresponding to their cluster of origin. Our findings illustrate the applicability of genotype databases for inferring hotspots of illegal capture and for guiding future reintroduction efforts, both of which are essential elements of species protection and recovery programs.
The genetics of situs inversus without primary ciliary dyskinesia
Authors: Postema Merel C. , Carrion-Castillo Amaia , Fisher Simon E. , Vingerhoets Guy , Francks Clyde
Published: February 2020

Situs inversus (SI), a left-right mirror reversal of the visceral organs, can occur with recessive Primary Ciliary Dyskinesia (PCD). However, most people with SI do not have PCD, and the etiology of their condition remains poorly studied. We sequenced the genomes of 15 people with SI, of which six had PCD, as well as 15 controls. Subjects with non-PCD SI in this sample had an elevated rate of left-handedness (five out of nine), which suggested possible developmental mechanisms linking brain and body laterality. The six SI subjects with PCD all had likely recessive mutations in genes already known to cause PCD. Two non-PCD SI cases also had recessive mutations in known PCD genes, suggesting reduced penetrance for PCD in some SI cases. One non-PCD SI case had recessive mutations in PKD1L1, and another in CFAP52 (also known as WDR16). Both of these genes have previously been linked to SI without PCD. However, five of the nine non-PCD SI cases, including three of the left-handers in this dataset, had no obvious monogenic basis for their condition. Environmental influences, or possible random effects in early development, must be considered.
A xylan glucuronosyltransferase gene exhibits pleiotropic effects on cellular composition and leaf development in rice
Authors: Gao Dawei , Sun Wenqiang , Wang Dianwen , Dong Hualin , Zhang Ran , Yu Sibin
Published: February 2020

Leaf chlorophyll content is an important physiological indicator of plant growth, metabolism and nutritional status, and it is highly correlated with leaf nitrogen content and photosynthesis. In this study, we report the cloning and identification of a xylan glucuronosyltransferase gene (OsGUX1) that affects relative chlorophyll content in rice leaf. Using a set of chromosomal segment substitution lines derived from a cross of wild rice accession ACC10 and indica variety Zhenshan 97 (ZS97), we identified numerous quantitative trait loci for relative chlorophyll content. One major locus of them for relative chlorophyll content was mapped to a 10.3-kb region that contains OsGUX1. The allele OsGUX1AC from ACC10 significantly decreases nitrogen content and chlorophyll content of leaf compared with OsGUX1ZS from ZS97. The overexpression of OsGUX1 reduced chlorophyll content, and the suppression of this gene increased chlorophyll content of rice leaf. OsGUX1 is located in Golgi apparatus, and highly expressed in seedling leaf and the tissues in which primary cell wall synthesis occurring. Our experimental data indicate that OsGUX1 is responsible for addition of glucuronic acid residues onto xylan and participates in accumulation of cellulose and hemicellulose in the cell wall deposition, thus thickening the primary cell wall of mesophyll cells, which might lead to reduced chlorophyll content in rice leaf. These findings provide insights into the association of cell wall components with leaf nitrogen content in rice.
Author Correction: Vascular tortuosity of the internal carotid artery is related to the RNF213 c.14429G > A variant in moyamoya disease
Authors: An Sungjae , Kim Tackeun , Oh Chang Wan , Bang Jae Seung , Lee Si Un , Heo Jaehyuk
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Genomic alterations and abnormal expression of APE2 in multiple cancers
Authors: Jensen Katherine A. , Shi Xinghua , Yan Shan
Published: February 2020

Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.
Layer-specific sensory processing impairment in the primary somatosensory cortex after motor cortex infarction
Authors: Fukui Atsushi , Osaki Hironobu , Ueta Yoshifumi , Kobayashi Kenta , Muragaki Yoshihiro , Kawamata Takakazu , Miyata Mariko
Published: February 2020

Primary motor cortex (M1) infarctions sometimes cause sensory impairment. Because sensory signals play a vital role in motor control, sensory impairment compromises the recovery and rehabilitation of motor disability. However, the neural mechanism of the sensory impairment is poorly understood. We show that sensory processing in mouse primary somatosensory cortex (S1) was impaired in the acute phase of M1 infarctions and recovered in a layer-specific manner in the subacute phase. This layer-dependent recovery process and the anatomical connection pattern from M1 to S1 suggested that functional connectivity from M1 to S1 plays a key role in the sensory processing impairment. A simulation study demonstrated that the loss of inhibition from M1 to S1 in the acute phase of M1 infarctions could impair sensory processing in S1, and compensation for the inhibition could recover the temporal coding. Consistently, the optogenetic activation of M1 suppressed the sustained response in S1. Taken together, we revealed how focal stroke in M1 alters the cortical network activity of sensory processing, in which inhibitory input from M1 to S1 may be involved.
Imaging active faulting in the western Taiwan Strait
Authors: Zhang Yifeng , Kuo-Chen Hao , Alvarez-Marron Joaquina , Brown Dennis , Lin Andrew Tien-Shun , Xie Zhizhao , Jin Xing
Published: February 2020

Large, destructive historical earthquakes off the coast of China’s Fujian Province point to important tectonic activity in the western Taiwan Strait that, until recently, has received little attention. We present newly acquired reflection seismic data that is used to study the shallow crustal structure of the western Taiwan Strait. With these data we map the location of the Benhai fault for the first time, describe its upper crustal geometry and, in combination with seismicity and earthquake focal mechanisms, interpret its kinematics. These new data demonstrate that there is wide spread evidence of faulting that reaches the sea floor in the western Taiwan Strait, clearly indicating that the Benhai fault is active. Faults that cut up section from steep basin sidewalls to form flower structures or terraced sidewall fault zones, together with the fault and basin map pattern, are consistent with this fault zone being in the early developmental stages of a dextral strike-slip system. Earthquake focal mechanisms, although not definitive, support the model of an active dextral strike-slip fault system in the western Taiwan Strait.
Identification of significant gene biomarkers of low back pain caused by changes in the osmotic pressure of nucleus pulposus cells
Authors: Zhao Changsong , Quan Xuemin , He Jie , Zhao Rugang , Zhang Yao , Li Xin , Sun Sheng , Ma Rui , Zhang Qiang
Published: February 2020

The incidence of intervertebral disc (IVD) degeneration disease, caused by changes in the osmotic pressure of nucleus pulposus (NP) cells, increases with age. In general, low back pain is associated with IVD degeneration. However, the mechanism and molecular target of low back pain have not been elucidated, and there are no data suggesting specific biomarkers of low back pain. Therefore, the research aims to identify and verify the significant gene biomarkers of low back pain. The differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database, and the identification and analysis of significant gene biomarkers were also performed with various bioinformatics programs. A total of 120 patients with low back pain were recruited. Before surgery, the degree of pain was measured by the numeric rating scale (NRS), which enables comparison of the pain scores from individuals. After surgery, IVD tissues were obtained, and NP cells were isolated. The NP cells were cultured in two various osmotic media, including iso-osmotic media (293 mOsm/kg H2O) to account for the morbid environment of NP cells in IVD degeneration disease and hyper-osmotic media (450 mOsm/kg H2O) to account for the normal condition of NP cells in healthy individuals. The relative mRNA expression levels of CCL5, OPRL1, CXCL13, and SST were measured by quantitative real-time PCR in thein vitroanalysis of the osmotic pressure experiments. Finally, correlation analysis and a neural network module were employed to explore the linkage between significant gene biomarkers and pain. A total of 371 DEGs were identified, including 128 downregulated genes and 243 upregulated genes. Furthermore, the four genes (CCL5, OPRL1, SST, and CXCL13) were identified as significant gene biomarkers of low back pain (P < 0.001) based on univariate linear regression, and CCL5 (odds ratio, 34.667; P = 0.003) and OPRL1 (odds ratio, 19.875; P < 0.001) were significantly related to low back pain through multivariate logistic regression. The expression of CCL5 and OPRL1 might be correlated with low back pain in patients with IVD degeneration disease caused by changes in the osmotic pressure of NP cells.
Variations in radioactive cesium accumulation in wheat germplasm from fields affected by the 2011 Fukushima nuclear power plant accident
Authors: Kubo Katashi , Kobayashi Hiroyuki , Nitta Miyuki , Takenaka Shotaro , Nasuda Shuhei , Fujimura Shigeto , Takagi Kyoko , Nagata Osamu , Ota Takeshi , Shinano Takuro
Published: February 2020

Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.
Treatment outcomes in acute invasive fungal rhinosinusitis extending to the extrasinonasal area
Authors: Nam Sung Hoon , Chung Yoo-Sam , Choi Young Jun , Lee Jeong Hyun , Kim Ji Heui
Published: February 2020

Acute invasive fungal rhinosinusitis (AIFRS) can spread beyond the sinonasal cavity. It is necessary to analyze the association between the specific site involved in the extrasinonasal area and the survival rate to predict patient prognosis. We investigated 50 patients who had extrasinonasal lesions on preoperative gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan and underwent wide surgical resection of AIFRS. The specific sites with loss of contrast enhancement (LoCE) on Gd-enhanced MRI were analyzed for AIFRS-specific survival rate. The most common underlying disease was diabetes mellitus followed by hematological malignancy. The most common symptoms were headache and facial pain. Seven patients (14.0%) expired because of AIFRS progression. Poor prognosis was independently associated with LoCE at the skull base on preoperative MRI (HR = 35.846, P = 0.004). In patients with AIFRS extending to the extrasinonasal area, LoCE at the skull base was an independent poor prognostic factor.
MRI Radiomic Features: Association with Disease-Free Survival in Patients with Triple-Negative Breast Cancer
Authors: Kim Sungwon , Kim Min Jung , Kim Eun-Kyung , Yoon Jung Hyun , Park Vivian Youngjean
Published: February 2020

Radiomic features hold potential to improve prediction of disease-free survival (DFS) in triple-negative breast cancer (TNBC) and may show better performance if developed from TNBC patients. We aimed to develop a radiomics score based on MRI features to estimate DFS in patients with TNBC. A total of 228 TNBC patients who underwent preoperative MRI and surgery between April 2012 and December 2016 were included. Patients were temporally divided into the training (n = 169) and validation (n = 59) set. Radiomic features of the tumor were extracted from T2-weighted and contrast-enhanced T1- weighted MRI. Then a radiomics score was constructed with the least absolute shrinkage and selection operator regression in the training set. Univariate and multivariate Cox proportional hazards models were used to determine what associations the radiomics score and clinicopathologic variables had with DFS. A combined clinicopathologic-radiomic (CCR) model was constructed based on multivariate Cox analysis. The incremental values of the radiomics score were evaluated by using the integrated area under the receiver operating characteristic curve (iAUC) and bootstrapping (n = 1000). The radiomics score, which consisted of 5 selected MRI features, was significantly associated with worse DFS in both the training and validation sets (p = 0.002, p = 0.033, respectively). In both the training and validation set, the radiomics score showed comparable performance with the clinicopathologic model. The CCR model demonstrated better performance than the clinicopathologic model in the training set (iAUC, 0.844; difference in iAUC, p < 0.001) and validation set (iAUC, 0.765, difference in iAUC, p < 0.001). In conclusion, MRI-based radiomic features can improve the prediction of DFS when integrated with clinicopathologic data in patients with TNBC.
Author Correction: Accelerated neuronal and synaptic maturation by BrainPhys medium increases Aβ secretion and alters Aβ peptide ratios from iPSC-derived cortical neurons
Authors: Satir Tugce Munise , Nazir Faisal Hayat , Vizlin-Hodzic Dzeneta , Hardselius Erik , Blennow Kaj , Wray Selina , Zetterberg Henrik , Agholme Lotta , Bergström Petra
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.