bluuebunny/crossref_metadata_2025 huggingface dataset:
Library of Congress: Early American Sheet Music
Authors: Robertson-Kirkland B. E.
Published: July 2018

Early American Sheet Music is a digital sheet-music collection curated and published by The Library of Congress. This beautiful resource provides open access to a specific classification number, M1.A1, by providing high-quality images and an easy-to-use visual browsing interface. It showcases early print sheet music and copied manuscripts from the United States and the colonies through 1820. However, the manner in which this digital collection has been curated highlights the changing roles and responsibilities of the library from custodian to custodian and publisher. While digital collections are enabling researchers across the world to see the resource, the curation tailors the online collection, thus invoking limitations on researchers. Further questions centre on issues of copyright. While the collection is free to use for personal research and education purposes, what persists is a constant confusion when it comes to downloading and performing early music found in digital collections. Performing such collections may be unique to music, but it is a serious issue that requires clarification. Using the new Early American Sheet Music resource as a centre for discussion, this article interrogates the current issues of digital music collections.
Documenting the Link Between Poor Food Access and Less Healthy Product Assortment Across the U.S.
Authors: Chenarides Lauren , Jaenicke Edward C.
Published: July 2018

This paper, which investigates food access and underserved areas in the U.S., differs from most existing research by explicitly examining food retailers' in‐store product availability, a retailing outcome that might exacerbate or mitigate consumer impacts of residing in areas with poor food access. Using detailed retailer scanner data from 2010–2015 and measures of food access, we investigate the relationship between healthy product assortments and food access. Our results consistently show a negative and significant relationship between census tracts with poor food access and healthy product assortments featuring fruits and vegetables. This finding provides rigorous documentation for what other researchers have claimed, namely that consumers who reside in underserved communities and are already burdened with poor food access endure the hardship of facing less healthy assortments of food items.
Surgical Breast Pocket Irrigation With Hypochlorous Acid (HOCl): An In Vivo Evaluation of Pocket Protein Content and Potential HOCl Antimicrobial Capacity
Authors: Haws Melinda J , Gingrass Mary K , Porter R Stephen , Brindle C Tod
Published: July 2018

Background

Hypochlorous acid (HOCl) demonstrates rapid and broad antimicrobial activity against planktonic and biofilm phenotype bacteria in vitro.

Objectives

To identify the protein content present in breast pockets in vivo and calculate the estimated active concentration of HOCl, (PhaseOne, Integrated Healing Technologies, Franklin, TN) following HOCl-protein interactions.

Methods

Fluid samples were collected prior to implant insertion in 18 consecutive patients, representing 36 pocket samples, with all cases being bilateral primary breast augmentations. Samples were evaluated by an independent CLIA approved laboratory for albumin and total protein concentration in g/dL. Results were compared to HOCl solution concentration and protein binding potential to determine availability of free HOCl.

Results

The mean tissue sample concentration (right and left breast) was 31.6 mg/dL which translates to 0.0001 mmol per 20 cc of interstitial fluid. Mean total protein levels (right and left breast) were 62.3 mg/dL or 0.000187 mmol per 20 cc interstitial fluid. Based upon potential stoichiometric neutralization of HOCl by proteins in either a 1:1 or 3:1 ratio, using 115 cc of HOCl solution (per breast) at a concentration of 250 ppm/mL or 0.025% HOCl or = 0.48 mmol HOCl/dL, there would be 2950 times the amount of active HOCl at a 1:1 reaction ratio, or 983 times more HOCl assuming a 3:1 reaction ratio. Based on the range of identified levels of protein in individual surgical pockets in the study, there is an estimated 242 to 12,500 times more HOCl molecules than protein at a 3:1 molar ratio of binding or reactive protein.

Conclusions

An estimated range of 983-2950 times more HOCl molecules are present during irrigation with 230 cc of PhaseOne® (115 cc for each breast) than available protein. This supports the antimicrobial and anti-biofilm activity as described in previous in vitro studies when using PhaseOne® as part of pocket irrigation.

Level of Evidence: 5
Safety and Efficacy of a Scar Cream Consisting of Highly Selective Growth Factors Within a Silicone Cream Matrix: A Double-Blinded, Randomized, Multicenter Study
Authors: Zoumalan Christopher I , Tadayon Shiva C , Roostaeian Jason , Rossi Anthony M , Gabriel Allen
Published: July 2018

Background

Several growth factors and hyaluronic acid are implicated in fetal scarless healing. Whether these factors can be applied to an adult scar to improve scar characteristics is unknown.

Objectives

This study compared the efficacy and safety of SKN2017B, a proprietary topical cream consisting of selective synthetic recombinant human growth factors and hyaluronic acid in a silicone base containing a specifically formulated silicone cream for postsurgical scar treatment.

Methods

In this prospective, randomized, controlled, double-blinded study, unilateral or bilateral facial or truncal scars in adult surgical patients were randomly treated with SKN2017B or silicone cream. Study investigators, study patients, and 2 independent reviewers assessed improvement in scar characteristics after 4 and 12 weeks of treatment.

Results

Forty-nine bilateral and 12 unilateral scars in 45 patients were treated with SKN2017B or silicone. At 12 weeks, investigators rated 74% of scars treated with SKN2017B as showing overall improvement vs 54% of silicone-treated scars, a 73% relative improvement with SKN2017B (P < 0.0001). Patients rated a moderate-to-significant improvement in 85% of SKN2017B-treated scars vs 51% of silicone-treated scars, a 67% relative improvement with SKN2017B (P < 0.001). Independent reviewers rated 87% of scars treated with SKN2017B to be better overall vs 1% of scars treated with silicone (P < 0.0001). There were no tolerability issues or adverse reactions with either cream.

Conclusions

SKN2017B consists of highly selective growth factors within a silicone cream matrix and is well tolerated and effective for surgical scar management.

Level of Evidence: 1
Resection of a Pediatric Intramedullary Spinal Cord Tumor: 2-Dimensional Operative Video
Authors: Woodroffe Royce W , Zanaty Mario , Kirby Patricia , Dlouhy Brian J , Menezes Arnold H
Published: July 2018

This video is a case presentation and demonstration of surgical approach to a pediatric intramedullary spinal cord tumor (IMSCT). IMSCT can be associated with significant morbidity and aggressive resection is associated with more favorable long-term outcome. A 13-yr-old male presented to clinic for evaluation of rapidly progressive scoliosis to the left. A contrasted MRI revealed expansion of the spinal cord with edema from approximately T3 to T9 and an enhancing lesion at T6-7 associated with a small cyst. On neurological exam, the patient had good strength throughout, but decreased sensation in the T7-12 dermatomes and decreased deep tendon reflexes in his lower extremities. The procedure included T5 to T8 osteoplastic laminectomies and IMSCT resection followed by spinal reconstruction. Intraoperative ultrasound was used to verify the tumor's location and somatosensory and motor evoked potentials were monitored throughout the procedure. Intraoperative consultation with neuropathology suggested the mass was likely pilocytic astrocytoma; therefore, it was aggressively debulked using microsurgical techniques including an ultrasonic aspirator. There was a plane between the tumor and spinal cord white matter allowing for a gross total resection. Postoperatively the patient had good strength throughout and sensation was intact except for continued numbness of the anterior thigh bilaterally. Immediate postoperative MRI demonstrated complete resection of the tumor without residual enhancement and the patient was ultimately discharged home on postoperative day 8. Follow-up imaging remained stable at 2 mo and the patient continued to do well neurologically. All patient identifiers were removed from the presented material, thus, patient consent was not obtained.
Results of Transcranial Resection of Olfactory Groove Meningiomas in Relation to Imaging-Based Case Selection Criteria for the Endoscopic Approach
Authors: Patel Krunal , Kolias Angelos G , Santarius Thomas , Mannion Richard J , Kirollos Ramez W
Published: July 2018

BACKGROUND

Endoscopic endonasal surgery (EES) is increasingly used for olfactory groove meningiomas (OGMs). The role of EES for large (≥4 cm) or complex OGMs is debated. Specific imaging features have been reported to affect the degree of gross total resection (GTR) and complications following EES for OGMs. The influence of these factors on transcranial resection (TCR) is unknown.

OBJECTIVE

To examine the impact of specific imaging features on outcome following TCR to provide a standard for large and endoscopically less favorable OGMs against which endoscopic outcomes can be compared.

METHODS

Retrospective study of patients undergoing TCR for OGMs 2002 to 2016.

RESULTS

Fifty patients (mean age 62.1 yr, mean maximum tumor diameter 5.04 cm and average tumor volume of 48.8 cm3) were studied. Simpson grade 1 and 2 resections were achieved in 80% and 12%, respectively. A favorable functional outcome (modified Rankin Scale [mRS] 0-2) was attained in 86%. The degree of resection, mRS, mortality (4%), recurrence (6%), infection (8%), and cerebrospinal fluid leak requiring intervention (12%) were not associated with tumor calcification, absence of cortical cuff, T2 hyperintensity, tumor configuration, tumor extension beyond midpoint of superior orbital roof, or extension to posterior wall of frontal sinus. There was no difference in resection rates but a trend towards greater complications between 3 arbitrarily divided groups of large meningiomas of increasing complexity based on extensive extension or vascular adherence.

CONCLUSION

Favorable outcomes can be achieved with TCR for large and complex OGMs Factors that may preclude endoscopic resection do not negatively affect outcome following TCR.
Pore‐forming toxin‐like protein complex expressed by frog promotes tissue repair
Authors: Gao Zhen-Hua , Deng Cheng-Jie , Xie Yue-Ying , Guo Xiao-Long , Wang Qi-Quan , Liu Ling-Zhen , Lee Wen-Hui , Li Sheng-An , Zhang Yun
Published: July 2018

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore‐forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. βγ‐crystallin fused aerolysin‐like protein (α‐subunit) and trefoil factor (β‐subunit) complex (βγ‐CAT) is a complex of a bacterial pore‐forming toxin aerolysin‐like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of βγ‐CAT on skin wound healing. βγ‐CAT accelerated the healing of full‐thickness wounds by improving re‐epithelialization. This complex relieved dermal edema and promoted scarless healing. βγ‐CAT treatment resulted in a rapid release of IL‐1β, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF‐β1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after βγ‐CAT treatment. βγ‐CAT protected skin wounds against methicillin‐resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that βγ‐CAT can promote tissue repair and protect skin wounds against antibiotic‐resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin‐like pore‐forming proteins widely existing in plants and animals may act in wound healing and tissue repair.—Gao, Z.‐H., Deng, C.‐J., Xie, Y.‐Y., Guo, X.‐L., Wang, Q.‐Q., Liu, L.‐Z., Lee, W.‐H., Li, S.‐A., Zhang, Y., Pore‐forming toxin‐like protein complex expressed by frog promotes tissue repair. FASEB J. 33, 782–795 (2019). www.fasebj.org
Systemic Inflammatory Markers Among Waterpipe Smokers, Cigarette Smokers, and Nonsmokers
Authors: Kumari Bhavita , Aslam Syeda Kanwal , Zaheer Sidra , Adil Syed Omair , Shafique Kashif
Published: July 2018

Objective:

To determine the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) among exclusive groups of waterpipe (WP) smokers, cigarette smokers, and nonsmokers.

Methods:

This cross-sectional study was conducted among adults, apparently healthy individuals, aged between 18 and 40 years of either gender. NLR and PLR as measures of systemic inflammation were studied in association with individuals’ sociodemographic, health, and tobacco use related characteristics. The results of linear and logistic regression models were reported as crude and adjusted beta coefficients and odds ratios with 95% confidence intervals (CIs).

Results:

Out of 190 participants, 34.2% (n = 65) exclusively smoked WP, 32.6% (n = 62) smoked cigarettes, and 33.2% (n = 63) were nonsmokers. The mean NLR and PLR were significantly higher among WP smokers when compared with nonsmokers; however, the comparison between WP smokers and cigarette smokers for both NLR and PLR was not statistically significant. The odds of raised NLR was 4.40 times higher (AOR = 4.40, 95% CI = 1.97, 9.85), and the odds of raised PLR was 3.48 times higher (AOR = 3.48, 95% CI = 1.60, 7.57) for WP smokers compared to nonsmokers.

Conclusions:

WP smoking has a significant association with systemic inflammation as measured by NLR and PLR. The study and existing evidence implicate an urging need to regulate WP industry and its policies.
Electromyographic Effect of Using Different Attentional Foci During the Front Plank Exercise
Authors: Calatayud Joaquin , Casaña Jose , Martín Fernando , Jakobsen Markus D. , Andersen Lars L. , Colado Juan Carlos
Published: July 2018

Objective

The aim of this cross-sectional study was to examine whether an internal focus on different core muscles during the isometric prone plank exercise increased muscle activity.

Design

Twenty university students performed the following five different conditions: regular prone plank (external focus) and prone plank with an internal focus on different muscles. Surface electromyography signals were recorded for the upper rectus abdominis, lower rectus abdominis, external oblique, and lumbar erector spinae.

Results

For the upper rectus abdominis, an internal focus on using any muscle increased activity. For the lower rectus abdominis, internal focus on any muscle except the lumbar erector spinae increased activity. No changes were found for external oblique and lumbar erector spinae activity.

Conclusions

Upper rectus abdominis and lower rectus abdominis activities increased during an internal focus on the abdominal muscles. external oblique and lumbar erector spinae activities were nonaffected by an internal focus on any muscle.
Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa
Authors: Velloza Jennifer , Baeten Jared M. , Haberer Jessica , Ngure Kenneth , Irungu Elizabeth , Mugo Nelly R. , Celum Connie , Heffron Renee ,   for the Partners Demonstration Project Team
Published: July 2018

Background:

Low adherence can undermine the efficacy of daily oral pre-exposure prophylaxis (PrEP). Mental health conditions, particularly depression, could be associated with low PrEP adherence, especially for women.

Setting:

We analyzed data from 1013 Kenyan and Ugandan HIV-uninfected participants in the Partners Demonstration Project, an open-label study of PrEP delivered to HIV-uninfected members of serodiscordant couples.

Methods:

Participants completed quarterly visits over 2 years and were encouraged to use PrEP until their partners living with HIV had ≥6 months of antiretroviral therapy use (when viral suppression was expected). PrEP adherence was measured daily with electronic medication event monitoring system caps and dichotomized into low (<80% of expected bottle openings) and high adherence. Depression was assessed annually using the 16-item Hopkins Symptom Checklist screening tool; scores >1.75 indicate “probable depression.” The association between probable depression and PrEP adherence was assessed separately for men and women using generalized estimating equations and marginal structural models.

Results:

At enrollment, 39 (11.7% of 334) women and 64 (9.4% of 679) men reported symptoms indicating probable depression, and these proportions decreased during follow-up (P < 0.001 for women and men). Probable depression was significantly associated with low PrEP adherence among women (adjusted risk ratio = 1.77; 95% confidence interval: 1.14 to 2.77; P = 0.01); there was no association between depression and adherence among men (P = 0.50). Marginal structural models and sensitivity analyses confirmed these findings.

Conclusions:

Depression was relatively uncommon in this population and was an independent risk factor for low PrEP adherence among women. For PrEP programs targeting African women, integration of depression screening may improve PrEP effectiveness.
Robust dynamical invariants in sequential neural activity
Authors: Elices Irene , Levi Rafael , Arroyo David , Rodriguez Francisco B. , Varona Pablo
Published: July 2018

By studying different sources of temporal variability in central pattern generator circuits, in this paper we unveil distinct aspects of the instantaneous balance between flexibility and robustness in sequential dynamics –a property that characterizes many systems that display neural rhythms. The level of irregularity and coordination was characterized using intrinsic time references and intervals in long recordings of the pyloric central pattern generator. The analysis demonstrated strong robustness of transient dynamics in keeping not only the activation sequences but also specific cycle-by-cycle temporal relationships in the form of dynamical invariants. The rich dynamics of neurons and connections balance flexibility and coordination to readily negotiate the interactions between neurons and produce the resultant rhythm. In particular, two dynamical invariants were identified between time intervals that build the sequence, existing even outside steady states. We suggest that invariant temporal sequence relationships could be present in other networks, including those related to brain rhythms, and underlie rhythm programming and functionality.
Torsional stress generated by ADF/cofilin on cross-linked actin filaments boosts their severing
Authors: Wioland Hugo , Jégou Antoine , Romet-Lemonne Guillaume
Published: July 2018

Proteins of the Actin Depolymerizing Factor (ADF)/cofilin family are the central regulators of actin filament disassembly. A key function of ADF/cofilin is to sever actin filaments. However, how it does so in a physiological context, where filaments are interconnected and under mechanical stress, remains unclear. Here, we monitor and quantify the action of ADF/cofilin in different mechanical situations by using single molecule, single filament, and filament network techniques, coupled to microfluidics. We find that local curvature favors severing, while tension surprisingly has no effect on either cofilin binding or severing. Remarkably, we observe that filament segments that are held between two anchoring points, thereby constraining their twist, experience a mechanical torque upon cofilin binding. We find that this ADF/cofilin-induced torque does not hinder ADF/cofilin binding, but dramatically enhances severing. A simple model, which faithfully recapitulates our experimental observations, indicates that the ADF/cofilin-induced torque increases the severing rate constant 100-fold. A consequence of this mechanism, which we verify experimentally, is that cross-linked filament networks are severed by cofilin far more efficiently than non-connected filaments. We propose that this mechano-chemical mechanism is critical to boost ADF/cofilin’s ability to sever highly connected filament networks in cells.
The macrocyclizing protease butelase 1 remains auto-catalytic and reveals the structural basis for ligase activity
Authors: James Amy M. , Haywood Joel , Leroux Julie , Ignasiak Katarzyna , Elliott Alysha G. , Schmidberger Jason W. , Fisher Mark F. , Nonis Samuel G. , Fenske Ricarda , Bond Charles S. , Mylne Joshua S.
Published: July 2018

Plant asparaginyl endopeptidases (AEPs) are expressed as inactive zymogens that perform seed storage protein maturation upon cleavage dependent auto-activation in the low pH environment of storage vacuoles. AEPs have attracted attention for their macrocyclization reactions and have been classified as cleavage or ligation specialists. However, we have recently shown that the ability of AEPs to produce either cyclic or acyclic products can be altered by mutations to the active site region, and that several AEPs are capable of macrocyclization given favorable pH conditions. One AEP extracted from Clitoria ternatea seeds (butelase 1) is classified as a ligase rather than a protease, presenting an opportunity to test for loss of cleavage activity. Here, making recombinant butelase 1 and rescuing an Arabidopsis thaliana mutant lacking AEP, we show butelase 1 retains cleavage functions in vitro and in vivo. The in vivo rescue was incomplete, consistent with some trade-off for butelase 1 specialization toward macrocyclization. Its crystal structure showed an active site with only subtle differences from cleaving AEPs, suggesting the many differences in its peptide binding region are the source of its efficient macrocyclization. All considered, it seems either butelase 1 has not fully specialized or a requirement for auto-catalytic cleavage is an evolutionary constraint upon macrocyclizing AEPs.
Brain dynamics and temporal trajectories during task and naturalistic processing
Authors: Venkatesh Manasij , Jaja Joseph , Pessoa Luiz
Published: July 2018

Human functional Magnetic Resonance Imaging (fMRI) data are acquired while participants engage in diverse perceptual, motor, cognitive, and emotional tasks. Although data are acquired temporally, they are most often treated in a quasi-static manner. Yet, a fuller understanding of the mechanisms that support mental functions necessitates the characterization of dynamic properties. Here, we describe an approach employing a class of recurrent neural networks called reservoir computing, and show the feasibility and potential of using it for the analysis of temporal properties of brain data. We show that reservoirs can be used effectively both for condition classification and for characterizing lower-dimensional “trajectories” of temporal data. Classification accuracy was approximately 90% for short clips of “social interactions” and around 70% for clips extracted from movie segments. Data representations with 12 or fewer dimensions (from an original space with over 300) attained classification accuracy within 5% of the full data. We hypothesize that such low-dimensional trajectories may provide “signatures” that can be associated with tasks and/or mental states. The approach was applied across participants (that is, training in one set of participants, and testing in a separate group), showing that representations generalized well to unseen participants. Taken together, we believe the present approach provides a promising framework to characterize dynamic fMRI information during both tasks and naturalistic conditions.
Connectivity dynamics from wakefulness to sleep
Authors: Damaraju Eswar , Tagliazucchi Enzo , Laufs Helmut , Calhoun Vince D
Published: July 2018

Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 seconds, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.
Predicting Negative Control Drugs to Support Research in Drug Safety
Authors: Hao Yun , Tatonetti Nicholas P.
Published: July 2018

The lack of high-quality reference data is a major limitation in drug safety and drug discovery science. Unreliable standards prohibit the use of supervised learning methods and make evaluation of algorithms difficult. While some data is available for positive examples (e.g. which drugs are associated with a side effect), there are no systematic resources of negative controls. To solve this issue, we introduced SIDERctrl, a computational method that ranks drugs based on the likelihood of not causing a side effect. We applied SIDERctrl to predict negative controls from unreported drugs of 890 side effects in SIDER. Our predictions decreased the false negative rate by one-third according to a validation study using AEOLUS data. Three sets of predicted negative controls by different thresholds of precision were provided, and can be accessed at http://tatonettilab.org/resources/negative-drugs.html. This new reference standard will be important in chemical biology, drug development, and pharmacoepidemiology.

KEY POINTS

The lack of systematic resources providing negative control drugs limits the performance of existing research in drug safety.

We developed a novel method that integrated chemical and biological properties a drug and the target proteins to calculate the likelihood of the drug being negative control.

We applied our method to 890 side effects, and showed that our method significantly decreased the false negative rate of predictions.
Analysis of microbial community structure of pit mud for Chinese strong-flavor liquor fermentation using next generation DNA sequencing of full-length 16S rRNA
Authors: Liu Zuolin , Han Ying , Li Junwei , Cao Runjie , He Hongkui , Li Anjun , Zhang Zhizhou
Published: July 2018

The pit is the necessary bioreactor for brewing process of Chinese strong-flavor liquor. Pit mud in pits contains a large number of microorganisms and is a complex ecosystem. The analysis of bacterial flora in pit mud is of great significance to understand liquor fermentation mechanisms. To overcome taxonomic limitations of short reads in 16S rRNA variable region sequencing, we used high-throughput DNA sequencing of near full-length 16S rRNA gene to analyze microbial compositions of different types of pit mud that produce different qualities of strong-flavor liquor. The results showed that the main species in pit mud were Pseudomonas extremaustralis 14-3, Pseudomonas veronii, Serratia marcescens WW4, and Clostridium leptum in Ruminiclostridium. The microbial diversity of pit mud with different quality was significantly different. From poor to good quality of pit mud (thus the quality of liquor), the relative abundances of Ruminiclostridium and Syntrophomonas in Firmicutes was increased, and the relative abundance of Olsenella in Actinobacteria also increased, but the relative abundances of Pseudomonas and Serratia in Proteobacteria were decreased. The surprising findings of this study include that the diversity of intermediate level quality of N pit mud was the lowest, and the diversity levels of high quality pit mud G and poor quality pit mud B were similar. Correlation analysis showed that there were high positive correlations (r > 0.8) among different microbial groups in the flora. Based on the analysis of the microbial structures of pit mud in different quality, the good quality pit mud has a higher microbial diversity, but how this higher diversity and differential microbial compositions contribute to better quality of liquor fermentation remains obscure.
Measuring cis-regulatory energetics in living cells using allelic manifolds
Authors: Forcier Talitha , Ayaz Andalus , Gill Manraj S. , Jones Daniel , Phillips Rob , Kinney Justin B.
Published: July 2018

Gene expression in all organisms is controlled by cooperative interactions between DNA-bound transcription factors (TFs), but quantitatively measuring TF-DNA and TF-TF interactions remains difficult. Here we introduce a strategy for precisely measuring the Gibbs free energy of such interactions in living cells. This strategy centers on the measurement and modeling of “allelic manifolds”, a multidimensional generalization of the classical genetics concept of allelic series. Allelic manifolds are measured using reporter assays performed on strategically designed cis-regulatory sequences. Quantitative biophysical models are then fit to the resulting data. We used this strategy to study regulation by twoEscherichia coliTFs, CRP and σ70RNA polymerase. Doing so, we consistently obtained energetic measurements precise to ~ 0.1 kcal/mol. We also obtained multiple results that deviate from the prior literature. Our strategy is compatible with massively parallel reporter assays in both prokaryotes and eukaryotes, and should therefore be highly scalable and broadly applicable.
Ramping and phasic dopamine activity accounts for efficient cognitive resource allocation during reinforcement learning
Authors: Song Minryung R. , Lee Sang Wan
Published: July 2018

Dopamine activity may transition between two patterns: phasic responses to reward-predicting cues and ramping activity arising when an agent approaches the reward. However, when and why dopamine activity transitions between these modes is not understood. We hypothesize that the transition between ramping and phasic patterns reflects resource allocation which addresses the task dimensionality problem during reinforcement learning (RL). By parsimoniously modifying a standard temporal difference (TD) learning model to accommodate a mixed presentation of both experimental and environmental stimuli, we simulated dopamine transitions and compared it with experimental data from four different studies. The results suggested that dopamine transitions from ramping to phasic patterns as the agent narrows down candidate stimuli for the task; the opposite occurs when the agent needs to re-learn candidate stimuli due to a value change. These results lend insight into how dopamine deals with the tradeoff between cognitive resource and task dimensionality during RL.
Effects of depression on prefrontal-striatal goal-directed and habitual control
Authors: Heo Suyeon , Lee Sang Wan
Published: July 2018

Depression is characterized by deficits in the reinforcement learning (RL) process. Although many computational and neural studies have extended our knowledge of the impact of depression on RL, most focus on habitual control (model-free RL), yielding a relatively poor understanding of goal-directed control (model-based RL) and arbitration control to find a balance between the two. We investigate the effects of depression on goal-directed and habitual control in the prefrontal–striatal circuitry. We find that depression is associated with attenuated state and reward prediction error representation in the insula and caudate, a disruption of arbitration control in the predominantly inferior lateral prefrontal cortex and frontopolar cortex, and suboptimal value–action conversion. These findings fully characterize how depression influences different levels of RL, challenging previous conflicting views that depression simply influences either habitual or goal-directed control. Our study creates possibilities for various clinical applications, such as early diagnosis and behavioral therapy design.
Lewis rat NLRP1 inflammasome activation is mediated by threeToxoplasma gondiidense granule proteins
Authors: Wang Yifan , Cirelli Kimberly M. , Barros Patricio D.C. , Sangaré Lamba Omar , Butty Vincent , Hassan Musa A. , Pesavento Patricia , Mete Asli , Saeij Jeroen P.J.
Published: July 2018

The Lewis rat is the only known warm-blooded animal that has sterile immunity toToxoplasma. Upon invasion of Lewis rat macrophagesToxoplasmarapidly activates the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 1 (NLRP1) inflammasome resulting in interleukin (IL)-1β secretion and a form of cell death known as pyroptosis, which preventsToxoplasmareplication. Using a chemical mutagenesis screen we identifiedToxoplasmamutants that no longer induced pyroptosis. Whole genome sequencing led to the identification of threeToxoplasmaparasitophorous vacuole-localized dense granule proteins, GRA35, GRA42 and GRA43 that are individually required for inflammasome activation in Lewis rat macrophages. Macrophage infection with Δgra35, Δgra42, and Δgra43parasites leads to greatly reduced cell death and reduced IL-1β secretion. Lewis rat macrophage infected with parasites containing single, double or triple deletion of these GRAs showed similar levels of cell viability suggesting the three GRAs function in the same pathway that activates the inflammasome. Deletion ofGRA42andGRA43resulted in GRA35, and other GRAs, being retained inside the parasitophorous vacuole instead of being localized to the parasitophorous vacuole membrane.Toxoplasmadeficient in GRA35, GRA42 or GRA43 do not establish chronic infection in Lewis rats, but have reduced cyst number in parasite-susceptible F344 rats, in whichToxoplasmadoes not activate the NLRP1 inflammasome, revealing these GRAs determine parasitein vivofitness independent of their role in inflammasome activation. Overall, our data suggest thatToxoplasmadense granule proteins that localize to the parasitophorous vacuole membrane are novel mediators of host NLRP1 inflammasome activation.

Importance

Inflammasomes are a major component of the innate immune system and responsible for detecting various microbial and environmental danger signals. The Lewis rat has sterile immunity toToxoplasmabecause upon invasion of Lewis rat macrophages the parasite rapidly activates the NLRP1 inflammasome resulting in cell death and parasite elimination. The work reported here identified thatToxoplasmaGRA35, GRA42 and GRA43 are required for activation of the Lewis rat NLRP1 inflammasome. GRA42 and GRA43 mediate the correct localization of other GRAs, including GRA35, to the parasitophorous vacuole membrane. In addition to their role in inflammasome activation, these three GRAs are also important for parasitein vivofitness in aToxoplasma-susceptible rat strain. Thus, these results give new insight into NLRP1 inflammasome activation byToxoplasmaeffectors and identified three GRAs that are required for pathogenesis of the parasite.
Mnemonic introspection in macaques is dependent on dorsolateral prefrontal cortex but not orbitofrontal cortex
Authors: Kwok Sze Chai , Cai Yudian , Buckley Mark J.
Published: July 2018

The human prefrontal cortex (PFC) has been associated more with meta-perceptual as opposed to meta-memory decisions from correlational neuroimaging investigations. Recently, metacognitive abilities have also been shown to be causally dependent upon anterior and dorsal PFC in non-human primate lesion studies. Two studies, utilizing post-decision wagering paradigms and reversible inactivation, challenged this meta-perceptual versus meta-memory notion and showed that dorsal and anterior prefrontal areas are associated with metamemory for experienced objects and awareness of ignorance respectively. Causal investigations are important but scarce; nothing is known, for example, about the causal contributions of prefrontal sub-regions to spatial metamemory. Here, we investigated the effects of dorsal versus ventral PFC lesions on two-alternative forced choice spatial discrimination tasks in male macaque monkeys. Importantly, we were rigorous in approach and applied three independent but complementary indices used to quantify individual animals’ metacognitive ability (“type II sensitivity”) namelymeta-d′, d′ measures, and Phi coefficient (Φ). Our results were consistent across indices: while neither lesions to superior dorsolateral PFC (sdlPFC) nor orbitofrontal cortex (OFC) impaired spatial recognition performance, only monkeys with sdlPFC lesions were impaired in meta-accuracy. Together with the observation that the same OFC lesioned monkeys were impaired in updating rule-value in a Wisconsin Card Sorting Test analog, we therefore document a functional double-dissociation between these two PFC regions. Out study presents important causal evidence that other dimensions, namely domain-specific processing (e.g., spatial versus non-spatial metamemory), also need considerations in understanding the functional specialization in the neural underpinnings of introspection.

Significance Statement

This study demonstrates macaque monkeys’ meta-cognitive capability of introspecting its own memory success is causally dependent on intact superior dorsolateral prefrontal cortices (PFC) but not the orbitofrontal cortices. Combining neurosurgical techniques on monkeys and state-of-the-art measures of metacognition, we affirm a critical role of the PFC in supporting spatial meta-recognition memory and delineate functional specificity within PFC for distinct elements of metacognition.
Coherent-hybrid STED: a tunable photo-physical pinhole for super-resolution imaging at high contrast
Authors: Pereira António J. , Sousa Mafalda , Almeida Ana C. , Ferreira Luísa T. , Costa Ana Rita , Novais-Cruz Marco , Ferrás Cristina , Sousa Mónica Mendes , Sampaio Paula , Belsley Michael , Maiato Helder
Published: July 2018

Resolution in microscopy is not limited by diffraction as long as a nonlinear sample response is exploited. In a paradigmatic example, stimulated-emission depletion (STED) fluorescence microscopy fundamentally ‘breaks’ the diffraction limit by using a structured optical pattern to saturate depletion on a previously excited sample area. Two-dimensional (2D) STED, the canonical low-noise STED mode, structures the STED beam by using a vortex phase mask, achieving a significant lateral resolution improvement over confocal fluorescence microscopy. However, axial resolution and optical sectioning remain bound to diffraction. Here we use a tunable coherent-hybrid (CH) beam to improve optical sectioning, markedly reducing background fluorescence. CH-STED, which inherits the 2D-STED immunity to spherical aberration, diversifies the depletion strategy, allowing an optimal balance between two key metrics (lateral resolution and background suppression) to be found. CH-STED is used to perform high-contrast imaging of complex biological structures, such as the mitotic spindle and the neuron cell body.
Quantitative Interactome Proteomics Reveals a Molecular Basis for ATF6-Dependent Regulation of a Destabilized Amyloidogenic Protein
Authors: Plate Lars , Rius Bibiana , Nguyen Bianca , Genereux Joseph C. , Kelly Jeffery W. , Wiseman R. Luke
Published: July 2018

Activation of the unfolded protein response (UPR)-associated transcription factor ATF6 has emerged as a promising strategy to selectively reduce the secretion and subsequent toxic aggregation of destabilized, amyloidogenic proteins implicated in diverse systemic amyloid diseases. However, the molecular mechanism by which ATF6 activation reduces the secretion of amyloidogenic proteins remains poorly defined. Here, we establish a quantitative interactomics platform with improved throughput and sensitivity to define how ATF6 activation selectively reduces secretion of a destabilized, amyloidogenic immunoglobulin light chain (LC) associated with Light Chain Amyloidosis (AL). We show that ATF6 activation increases the targeting of this destabilized LC to a select subset of pro-folding ER proteostasis factors that retains the amyloidogenic LC within the ER, preventing its secretion to downstream secretory environments. Our results define a molecular basis for the selective, ATF6-dependent reduction in destabilized LC secretion and highlight the advantage for targeting this endogenous UPR-associated transcription factor to reduce secretion of destabilized, amyloidogenic proteins implicated in AL and related systemic amyloid diseases.
Single-cell copy number variant detection reveals the dynamics and diversity of adaptation
Authors: Lauer Stephanie , Avecilla Grace , Spealman Pieter , Sethia Gunjan , Brandt Nathan , Levy Sasha , Gresham David
Published: July 2018

Copy number variants (CNVs) are a pervasive, but understudied source of genetic variation and evolutionary potential. Long-term evolution experiments in chemostats provide an ideal system for studying the molecular processes underlying CNV formation and the temporal dynamics ofde novoCNVs. Here, we developed a fluorescent reporter to monitor gene amplifications and deletions at a specific locus with single-cell resolution. Using a CNV reporter in nitrogen-limited chemostats, we find thatGAP1CNVs are repeatedly generated and selected during the early stages of adaptive evolution resulting in predictable dynamics of CNV selection. However, subsequent diversification of populations defines a second phase of evolutionary dynamics that cannot be predicted. Using whole genome sequencing, we identified a variety ofGAP1CNVs that vary in size and copy number. DespiteGAP1’s proximity to tandem repeats that facilitate intrachromosomal recombination, we find that non-allelic homologous recombination (NAHR) between flanking tandem repeats occurs infrequently. Rather, breakpoint characterization revealed that for at least 50% ofGAP1CNVs, origin-dependent inverted-repeat amplification (ODIRA), a DNA replication mediated process, is the likely mechanism. We also find evidence that ODIRA generatesDUR3CNVs, indicating that it may be a common mechanism of gene amplification. We combined the CNV reporter with barcode lineage tracking and found that 103-104independent CNV-containing lineages initially compete within populations, which results in extreme clonal interference. Our study introduces a novel means of studying CNVs in heterogeneous cell populations and provides insight into the underlying dynamics of CNVs in evolution.
The Cdc42 GEF, Gef1, promotes uniform protein distribution along the actomyosin ring to enable concentric furrowing
Authors: Onwubiko Udodirim , Mlynarczyk Paul J. , Wei Bin , Habiyaremye Julius , Clack Amanda , Abel Steven M. , Das Maitreyi E.
Published: July 2018

During cytokinesis, fission yeast coordinates actomyosin ring constriction with septum ingression, resulting in concentric furrow formation. Mechanisms coordinating septum ingression with the actomyosin ring remain unclear. We report that cells lacking the Cdc42 activator Gef1, combined with an activated allele of the formin, Cdc12, display non-concentric furrowing. Although cells that furrow non-concentrically display normal actomyosin rings, the scaffold Cdc15 is unevenly distributed along the ring. This suggests that after ring assembly, uniform Cdc15 distribution along the ring drives proper furrow formation. We find that Cdc15 levels at the ring are reduced in the activatedcdc12mutant, or upon disruption of Arp2/3 complex-dependent endocytic patches. Furthermore, Cdc15 levels in endocytic patches increase ingef1mutants. We hypothesize that assembled rings recruit Cdc15 from endocytic patches. Patches with higher Cdc15 levels and slower ring-association rate lead to uneven Cdc15 distribution. Based on this hypothesis we developed a mathematical model that captures experimentally observed Cdc15 distributions along the ring. We propose that, at the ring, Gef1 and endocytic events promote uniform Cdc15 distribution to enable proper septum ingression and concentric furrow formation.

Summary Statement

Gef1 and endocytic events at the assembled actomyosin ring facilitate uniform Cdc15 distribution along the ring thus enabling concentric furrow formation.
Cluster analysis for fruit consumption patterns: an international study
Authors: Heng Yan , House Lisa A.
Published: July 2018

Purpose

The purpose of this paper is to investigate the fruit consumer segmentations and compare the consumption patterns across North America, Europe and East Asia. This study aims to identify the key drivers for fruit consumption across segments and regions, in terms of socioeconomics and shopping behavior.

Design/methodology/approach

An international survey to collect information on fruit consumption, demographics and lifestyle factors was developed. Respondents from eight countries across North America, Europe and East Asia were recruited from online panels. A total usable sample of 7,793 respondents was collected.

Findings

Respondents can be clustered in three segments: low-frequency consumer, common fruit consumer and high-frequency consumer. These consumer segments are heterogeneous in socioeconomics and shopping behavior across regions. Overall, the high-frequency consumer cluster had more individuals who were older, married, not single/never married, self-reported healthy and physically active. The low-frequency consumer group had a larger number of individuals who were younger, living alone, single/never married, self-reported unhealthy and not active. Moreover, the high-frequency fruit consumers tended to focus on many fruit attributes, such as freshness, nutritional value, origin and in the season, but not focus on the price.

Originality/value

This study uses a unique data set covering eight countries and provides a comprehensive comparison of international fruit consumption patterns and identifying the important factors driving fruit purchase decisions.