bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-seq Analysis Reveals Mitochondrial and Cuticular Protein Genes Are Associated with Phosphine Resistance in the Rusty Grain Beetle (Coleoptera:Laemophloeidae)
Authors: Chen Er-Hu , Duan Jin-Yan , Song Wei , Wang Dian-Xuan , Tang Pei-An
Published: November 2020

The rusty grain beetle, Cryptolestes ferrugineus (Stephens), is a serious pest of stored grain, which has developed high levels of resistance to phosphine. In this study, five geographically distant populations of C. ferrugineus had been collected in China, specifically in granaries where phosphine fumigant is used for pest control, and they showed a high resistance ratio up to 1,907 (LC50 = 21.0 mg/liter). Then, a reference transcriptome was constructed to use as a basis for investigating the molecular mechanisms of phosphine resistance in this species, which consisted of 47,006 unigenes with a mean length of 1,090. Subsequently, the RNA-Seq analysis of individuals from the most susceptible and resistant populations led to the identification of 54 genes that are differentially expressed. GO and KEGG analysis demonstrated that genes associated with mitochondrial and respiration functions were significantly enriched. Also, the ‘structural constituent of cuticle’ term was annotated in the GO enrichment analysis and further qRT-PCR confirmed that the expression levels of nine cuticular protein genes were significantly increased in the resistant population. In conclusion, we present here a transcriptome-wide overview of gene expression changes between resistant and susceptible populations of C. ferrugineus, and this in turn documents that mitochondria and cuticular protein genes may play together a crucial role in phosphine resistance. Further gene function analysis should enable the provision of advice to expedite resistance management decisions.
Visualizing textual similarity of Shakespearean suspect texts: An examination of the Henry VI plays
Authors: Kim Heejin
Published: November 2020

The relationship between Shakespeare’s First Folio and early printings, published in his lifetime, has been a matter of dispute for centuries. A computer program that I have developed visualizes the fluctuating quality of textual correspondences between Folio texts, Henry the Sixth, Part Two and Three, and texts that have been suspected as memorial reconstructions of the Folio, The First Part of the Contention and The True Tragedy of Richard Duke of York. The memorial reconstruction hypothesis assumes increased similarity between the two texts when an alleged actor–reporter is on the stage or speaking and vice versa. The visualization of similarity between two texts, based on the Dice similarity metric, does not show a strong association between the fluctuation of similarity and actor–reporter factors, which challenges the memorial reconstruction hypothesis on statistical grounds. In addition, the distribution of line-by-line similarity scores suggests scene division is a considerable explanatory factor for fluctuating similarity, which is not inexplicable, considering the practice of collaborative writing in the early modern playhouse.
The transcriptional repressors VAL1 and VAL2 recruit PRC2 for genome-wide Polycomb silencing in Arabidopsis
Authors: Yuan Liangbing , Song Xin , Zhang Lu , Yu Yaoguang , Liang Zhenwei , Lei Yawen , Ruan Jiuxiao , Tan Bin , Liu Jun , Li Chenlong
Published: November 2020

The Polycomb repressive complex 2 (PRC2) catalyzes histone H3 Lys27 trimethylation (H3K27me3) to repress gene transcription in multicellular eukaryotes. Despite its importance in gene silencing and cellular differentiation, how PRC2 is recruited to target loci is still not fully understood. Here, we report genome-wide evidence for the recruitment of PRC2 by the transcriptional repressors VIVIPAROUS1/ABI3-LIKE1 (VAL1) and VAL2 in Arabidopsis thaliana. We show that the val1 val2 double mutant possesses somatic embryonic phenotypes and a transcriptome strikingly similar to those of the swn clf double mutant, which lacks the PRC2 catalytic subunits SWINGER (SWN) and CURLY LEAF (CLF). We further show that VAL1 and VAL2 physically interact with SWN and CLF in vivo. Genome-wide binding profiling demonstrated that they colocalize with SWN and CLF at PRC2 target loci. Loss of VAL1/2 significantly reduces SWN and CLF enrichment at PRC2 target loci and leads to a genome-wide redistribution of H3K27me3 that strongly affects transcription. Finally, we provide evidence that the VAL1/VAL2–RY regulatory system is largely independent of previously identified modules for Polycomb silencing in plants. Together, our work demonstrates an extensive genome-wide interaction between VAL1/2 and PRC2 and provides mechanistic insights into the establishment of Polycomb silencing in plants.
Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins
Authors: Ren Xiangle , Zhou Yang , Xue Zhaoyu , Hao Ning , Li Yuanyuan , Guo Xiaohuan , Wang Daliang , Shi Xiaobing , Li Haitao
Published: November 2020

Histone modifications and their functional readout serve as an important mechanism for gene regulation. Lysine benzoylation (Kbz) on histones is a recently identified acylation mark associated with active transcription. However, it remains to be explored whether putative readers exist to recognize this epigenetic mark. Here, our systematic binding studies demonstrated that the DPF and YEATS, but not the Bromodomain family members, are readers for histone Kbz. Co-crystal structural analyses revealed a ‘hydrophobic encapsulation’ and a ‘tip-sensor’ mechanism for Kbz readout by DPF and YEATS, respectively. Moreover, the DPF and YEATS family members display subtle yet unique features to create somewhat flexible engagements of different acylation marks. For instance, YEATS2 but not the other YEATS proteins exhibits best preference for Kbz than lysine acetylation and crotonylation due to its wider ‘tip-sensor’ pocket. The levels of histone benzoylation in cultured cells or in mice are upregulated upon sodium benzoate treatment, highlighting its dynamic regulation. In summary, our work identifies the first readers for histone Kbz and reveals the molecular basis underlying Kbz recognition, thus paving the way for further functional dissections of histone benzoylation.
An RNA pseudoknot is essential for standby-mediated translation of thetisBtoxin mRNA inEscherichia coli
Authors: Romilly Cédric , Lippegaus Anne , Wagner E Gerhart H
Published: November 2020

In response to DNA damage, Escherichia coli cells activate the expression of the toxin gene tisB of the toxin–antitoxin system tisB-istR1. Of three isoforms, only the processed, highly structured +42 tisB mRNA is active. Translation requires a standby site, composed of two essential elements: a single-stranded region located 100 nucleotides upstream of the sequestered RBS, and a structure near the 5′-end of the active mRNA. Here, we propose that this 5′-structure is an RNA pseudoknot which is required for 30S and protein S1-alone binding to the mRNA. Point mutations that prevent formation of this pseudoknot inhibit formation of translation initiation complexes, impair S1 and 30S binding to the mRNA, and render the tisB mRNA non-toxic in vivo. A set of mutations created in either the left or right arm of stem 2 of the pseudoknot entailed loss of toxicity upon overexpression of the corresponding mRNA variants. Combining the matching right-left arm mutations entirely restored toxicity levels to that of the wild-type, active mRNA. Finally, since many pseudoknots have high affinity for S1, we predicted similar pseudoknots in non-homologous type I toxin–antitoxin systems that exhibit features similar to that of tisB-IstR1, suggesting a shared requirement for standby acting at great distances.
A fast and robust iterative genome-editing method based on a Rock-Paper-Scissors strategy
Authors: Wang Jichao , Sui Xinyue , Ding Yamei , Fu Yingxin , Feng Xinjun , Liu Min , Zhang Youming , Xian Mo , Zhao Guang
Published: November 2020

The production of optimized strains of a specific phenotype requires the construction and testing of a large number of genome modifications and combinations thereof. Most bacterial iterative genome-editing methods include essential steps to eliminate selection markers, or to cure plasmids. Additionally, the presence of escapers leads to time-consuming separate single clone picking and subsequent cultivation steps. Herein, we report a genome-editing method based on a Rock-Paper-Scissors (RPS) strategy. Each of three constructed sgRNA plasmids can cure, or be cured by, the other two plasmids in the system; plasmids from a previous round of editing can be cured while the current round of editing takes place. Due to the enhanced curing efficiency and embedded double check mechanism, separate steps for plasmid curing or confirmation are not necessary, and only two times of cultivation are needed per genome-editing round. This method was successfully demonstrated in Escherichia coli and Klebsiella pneumoniae with both gene deletions and replacements. To the best of our knowledge, this is the fastest and most robust iterative genome-editing method, with the least times of cultivation decreasing the possibilities of spontaneous genome mutations.
Limited Clinical Utility of Follow-up Blood Cultures in Patients With Streptococcal Bacteremia: An Opportunity for Blood Culture Stewardship
Authors: Siegrist Emily A , Wungwattana Minkey , Azis Leyla , Stogsdill Patricia , Craig Wendy Y , Rokas Kristina E
Published: November 2020

Background

The value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia.

Methods

Adults ≥18 years of age, admitted with at least 1 positive blood culture for Streptococcus spp between 2013 and 2018 followed by at least 1 FUBC, were potentially eligible. Positive FUBCs were defined as cultures positive for the same streptococcal species drawn >24 hours after the index culture. We excluded patients with polymicrobial bacteremia. We compared the characteristics of patients with and without a positive FUBC.

Results

In our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Streptococcus spp (3.2%), 4 (1.3%) had a contaminant identified, and 3 (1.0%) had a new pathogen isolated. Endocarditis (5 of 10 [50.0%] vs 35 of 304 [11.5%]), epidural abscess (2 of 10 [20%] vs 4 of 304 [1.3%]), and discitis or vertebral osteomyelitis (3 of 10 [30.0%] vs 14 of 304 [4.6%]) were associated with positive FUBC. Patients with positive FUBC had a longer median length of stay (12.9 vs 7.1 days, P = .004) and longer duration of antibiotic treatment (14.9 vs 43.2 days, P = .03).

Conclusions

Follow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection.
Clinical Outcomes of Ceftriaxone vs Penicillin G for Complicated Viridans Group Streptococci Bacteremia
Authors: Wo Stephanie , Dubrovskaya Yanina , Siegfried Justin , Papadopoulos John , Jen Shin-Pung
Published: November 2020

Background

Ceftriaxone (CTX) and penicillin G (PCN G) are considered reasonable treatment options for viridans group streptococci (VGS) bloodstream infections, but comparisons between these agents are limited. We evaluated clinical outcomes among patients treated with these agents for complicated VGS bacteremia.

Methods

This was a single-center retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in the PCN arm) between January 2013 and June 2019. The primary outcome was a composite of safety end points, including hospital readmission due to VGS bacteremia or adverse events (AEs) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to AEs from therapy, and development of extended-spectrum beta-lactamase resistance. Secondary outcomes included individual safety end points, VGS bacteremia recurrence, hospital readmission, and all-cause mortality.

Results

Of 328 patients screened, 94 met eligibility criteria (CTX n = 64, PCN n = 30). Streptococcus mitis was the most common isolate, and infective endocarditis was the predominant source of infection. CTX was not significantly associated with increased risk of the primary composite safety outcome (CTX 14% vs PCN 27%; P = .139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. No secondary end points differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary composite safety outcome.

Conclusions

Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate higher rates of treatment failure, adverse events, or resistance.
Searching for periodic variations in radial velocities after the removal of orbital motions of spectroscopic binaries
Authors: Katoh Noriyuki , Itoh Yoichi , Sato Bun’ei
Published: November 2020

This study focuses on periodic variations of radial velocities (RVs) after removing the orbital motion of 33 spectroscopic binaries. The RVs were monitored from 2003 to 2012 and published in Katoh et al. (2013, AJ, 145, 41). Their RV precision was determined to be ∼10 m s−1 utilizing an I2 cell. We investigated the periodic variation using a generalzied Lomb–Scargle algorithm and found periodic variations in the residual velocities of seven binary systems. The residual-velocity variations are mostly generated by stellar activity rather than the orbital motion of a possible companion. For eight binaries, we found significant evidence of a second signal, with velocity dispersions greater than three times the RV uncertainty. We find these residual-velocity variations inconsistent with a Doppler signal induced by the orbital motion of an unknown component. For the remaining 18 binaries, we did not detect significant variations of residual-velocity.
A Retrospective Database Study of Gastrointestinal Events and Medical Costs Associated with Nonsteroidal Anti-Inflammatory Drugs in Japanese Patients of Working Age with Osteoarthritis and Chronic Low Back Pain
Authors: Kikuchi Shogo , Togo Kanae , Ebata Nozomi , Fujii Koichi , Yonemoto Naohiro , Abraham Lucy , Katsuno Takayuki
Published: November 2020

Context

The real-world burden of gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Japanese patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) remains unreported.

Objective

To assess the incidence and economic burden of NSAID-induced GI events by using data from large-scale real-world databases.

Methods

We used the Japanese Medical Data Center database to retrospectively evaluate anonymized claims data of medical insurance beneficiaries employed by middle- to large-size Japanese companies who were prescribed NSAIDs for OA and/or CLBP between 2009 and 2018.

Results

Overall, 180,371 patients were included in the analysis, of whom 32.9% had OA, 53.8% had CLBP, and 13.4% had both OA and CLBP. NSAIDs were administered as first-line analgesics to 161,152 (89.3%) of the patients in the sample, in oral form to 90.3% and as topical patches to 80.4%. A total of 65.1% used combined oral/topical patches. Of the 21.0% of patients consistently using NSAIDs (percentage of days supplied ≥70%), 54.5% received patches. A total of 51.5% patients used NSAIDs for >1 to ≤6 months. The incidence of GI events was 9.97 per 10,000 person-years (95% confidence interval: 8.92–11.03). The risk of developing GI events was high in elderly patients and patients with comorbidities and remained similar for patients receiving oral vs. topical NSAIDs. Longer treatment duration and consistent NSAID use increased the risk of GI events. The cost (median [interquartile range]) of medications (n = 327) was US$ 80.70 ($14.10, $201.40), that of hospitalization (n = 33) was US$ 2,035.50 ($1,517.80, $2,431.90), and that of endoscopic surgery (n = 52) was US$ 418.20 ($418.20, $418.20).

Conclusion

NSAID-associated GI toxicity imposes a significant health and economic burden on patients with OA and/or CLBP, irrespective of whether oral or topical NSAIDs are used.
The Style of the Old English Metrical Charms
Authors: Batten Caroline R.
Published: November 2020

The metre of the Old English metrical charms is highly unusual according to all postulated systems of Old English metrical scansion. Their numerous irregularities have led previous studies to dismiss the charms as corrupt or poor verse. The present study subjects the metrical charms to stylometric analysis for the first time and demonstrates that their irregularities are in fact both predictable and explicable. It argues that the charms are aesthetically sophisticated and vivid narrative poems, with stylistic features that complement their content. It demonstrates that their irregularities are a consequence of the accommodation of traditional formulae and plurilinear rhetorical structures evidently essential to these texts’ practical purposes and magical functions. The charms’ shared, unusual stylistic features suggest that they may represent a mode of Old English poetic composition distinct from the ‘classical’ verse found in texts like Beowulf, and the resulting re-evaluation of the charms’ aesthetic merit in turn suggests the importance of re-evaluating the criteria by which scholars judge Old English verse more broadly.
“Sorry, We're Closed” Bank Branch Closures, Loan Pricing, and Information Asymmetries
Authors: Bonfim Diana , Nogueira Gil , Ongena Steven
Published: November 2020

We study local loan conditions when banks close branches. In places where branch closures do not take place, firms that purposely switch banks receive a sixty-three basis points (bps) discount. However, after the closure of nearby branches of their credit-granting banks, firms that locally and hurriedly transfer to other banks receive no such discount. Yet, the loan default rate for the latter (more expensive) transfer loans is on average a full percentage point lower than that for the former (cheaper) switching loans. This suggests that transfer firms are of “better” quality than switching firms. In sum, even if local markets remain competitive, when banks close branches, firms lose.
Changes in EEG permutation entropy in the evening and in the transition from wake to sleep
Authors: Hou Fengzhen , Zhang Lulu , Qin Baokun , Gaggioni Giulia , Liu Xinyu , Vandewalle Gilles
Published: November 2020

Quantifying the complexity of the EEG signal during prolonged wakefulness and during sleep is gaining interest as an additional mean to characterize the mechanisms associated with sleep and wakefulness regulation. Here, we characterized how EEG complexity, as indexed by Multiscale Permutation Entropy (MSPE), changed progressively in the evening prior to light off and during the transition from wakefulness to sleep. We further explored whether MSPE was able to discriminate between wakefulness and sleep around sleep onset and whether MSPE changes were correlated with spectral measures of the EEG related to sleep need during concomitant wakefulness (theta power—Ptheta: 4–8 Hz). To address these questions, we took advantage of large datasets of several hundred of ambulatory EEG recordings of individual of both sexes aged 25–101 years. Results show that MSPE significantly decreases before light off (i.e. before sleep time) and in the transition from wakefulness to sleep onset. Furthermore, MSPE allows for an excellent discrimination between pre-sleep wakefulness and early sleep. Finally, we show that MSPE is correlated with concomitant Ptheta. Yet, the direction of the latter correlation changed from before light-off to the transition to sleep. Given the association between EEG complexity and consciousness, MSPE may track efficiently putative changes in consciousness preceding sleep onset. An MSPE stands as a comprehensive measure that is not limited to a given frequency band and reflects a progressive change brain state associated with sleep and wakefulness regulation. It may be an effective mean to detect when the brain is in a state close to sleep onset.
Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep
Authors: Harrington Marcus O , Ashton Jennifer E , Ngo Hong-Viet V , Cairney Scott A
Published: November 2020

Auditory closed-loop stimulation is a non-invasive technique that has been widely used to augment slow oscillations during non-rapid eye movement sleep. Based on the principles of closed-loop stimulation, we developed a novel protocol for manipulating theta activity (3–7 Hz) in rapid eye movement (REM) sleep. Sixteen healthy young adults were studied in two overnight conditions: Stimulation and Sham. In the Stimulation condition, 1 s of 5 Hz amplitude-modulated white noise was delivered upon detection of two supra-threshold theta cycles throughout REM sleep. In the Sham condition, corresponding time points were marked but no stimulation was delivered. Auditory stimulation entrained EEG activity to 5 Hz and evoked a brief (~0.5 s) increase in theta power. Interestingly, this initial theta surge was immediately followed by a prolonged (~3 s) period of theta suppression. Stimulation also induced a prolonged (~2 s) increase in beta power. Our results provide the first demonstration that the REM sleep theta rhythm can be manipulated in a targeted manner via auditory stimulation. Accordingly, auditory stimulation might offer a fruitful avenue for investigating REM sleep electrophysiology and its relationship to behavior.
Paired Double Consciousness: A Du Boisian Approach to Gender and Transnational Double Consciousness in Thai Kathoey Self-Formation
Authors: Lynne Alyssa
Published: November 2020

Sociologists have not adequately explored how Du Bois’ concept of double consciousness could be used to study the role of cisnormative oppression in self-formation or how it could enrich studies of self-formation beyond the Atlantic world. This article addresses these gaps by merging postcolonial feminist theory and the concept of double consciousness to analyze kathoey self-formation. Kathoey are gender nonconforming (GNC) individuals in Thailand who are assigned male at birth and live as women. Drawing upon participant observation, in-depth interviews, and content analysis, I propose an extension to double consciousness called “paired double consciousness.” This framework explains how cisnormative and neocolonial oppression lead kathoey to experience two veils. The first veil divides self-formation between kathoey and dominant cisgender worlds within Thai society, which produces “gender double consciousness.” The second veil divides self-formation between kathoey and dominant transgender worlds within a global community, which creates “transnational double consciousness.”
Animal sciences undergraduate education since the ASAS centennial: a national survey and scoping review
Authors: Erickson M G , Ranathunga S D , Wattiaux M A
Published: November 2020

The rapid pace of advancement in animal sciences is drastically changing conditions for undergraduate teaching and learning in the discipline. Shortly after the American Society of Animal Science (ASAS) centennial, we conducted a national survey of 90 faculty instructors from 49 academic institutions to assess their perceptions of emerging teaching topics. Participants rated 18 learning outcomes (LO) and 16 types of courses and experiences (CE) with respect to their importance and the adequacy of available offerings. This study presents the results of the survey along with a scoping review of animal sciences teaching and learning publications since 2008 (n = 71). Results indicated that discipline-specific competencies and core experiential learning remain central to animal sciences teaching and identified several distinct needs for research. Namely, we suggest that future research in animal sciences teaching and learning 1) develop animal-science-specific expertise on a greater variety of pedagogies, 2) validate improved methods for assessing transferable skills, 3) expand pedagogical knowledge of emerging topics (e.g., sustainability, data science, welfare science, social science), and 4) deepen and broaden animal sciences’ teaching and learning identity through theory-building work and collaborations across instructors, disciplines, and institutions.
An empirical example of analysis using a two-stage modeling approach: within-subject association of outdoor context and physical activity predicts future daily physical activity levels
Authors: Yang Chih-Hsiang , Maher Jaclyn P , Ponnada Aditya , Dzubur Eldin , Nordgren Rachel , Intille Stephen , Hedeker Donald , Dunton Genevieve F
Published: November 2020

People differ from each other to the extent to which momentary factors, such as context, mood, and cognitions, influence momentary health behaviors. However, statistical models to date are limited in their ability to test whether the association between two momentary variables (i.e., subject-level slopes) predicts a subject-level outcome. This study demonstrates a novel two-stage statistical modeling strategy that is capable of testing whether subject-level slopes between two momentary variables predict subject-level outcomes. An empirical case study application is presented to examine whether there are differences in momentary moderate-to-vigorous physical activity (MVPA) levels between the outdoor and indoor context in adults and whether these momentary differences predict mean daily MVPA levels 6 months later. One hundred and eight adults from a multiwave longitudinal study provided 4 days of ecological momentary assessment (during baseline) and accelerometry data (both at baseline and 6 month follow-up). Multilevel data were analyzed using an open-source program (MixWILD) to test whether momentary strength between outdoor context and MVPA during baseline was associated with average daily MVPA levels measured 6 months later. During baseline, momentary MVPA levels were higher in outdoor contexts as compared to indoor contexts (b = 0.07, p < .001). Participants who had more momentary MVPA when outdoors (vs. indoors) during baseline (i.e., a greater subject-level slope) had higher daily MVPA at the 6 month follow-up (b = 0.09, p < .05). This empirical example shows that the subject-level momentary association between specific context (i.e., outdoors) and health behavior (i.e., physical activity) may contribute to overall engagement in that behavior in the future. The demonstrated two-stage modeling approach has extensive applications in behavioral medicine to analyze intensive longitudinal data collected from wearable sensors and mobile devices.
L-carnitine suppresses cisplatin-induced renal injury in rats: impact on cytoskeleton proteins expression
Authors: Ebrahim Osama Fouad Ahmed , Nafea Ola Elsayed , Samy Walaa , Shawky Lamiaa Mohamed
Published: November 2020

We designed this work to examine the curative role of L-carnitine (LCAR) in a rat model of cisplatin (CDDP)-induced kidney injury. We induced kidney injury in rats by a single intraperitoneal injection of 5 mg/kg of CDDP. Fifteen days post injection, rats were orally supplemented with 354 mg/kg of LCAR for another 15 days. Kidney tissues were subjected to histo-biochemical analysis along with mRNA gene expression quantification for cytoskeleton proteins encoding genes (vimentin, nestin, and connexin 43) by real-time reverse transcription polymerase chain reaction. LCAR reversed CDDP-induced renal structural and functional impairments. LCAR significantly declined serum urea and creatinine concentrations, restored oxidant/antioxidant balance, reversed inflammation, and antagonized caspase 3-mediated apoptotic cell death in renal tissues. Moreover, LCAR effectively down-regulated cytoskeleton proteins mRNA levels, reflecting amelioration of CDDP-provoked podocyte injury. We concluded that LCAR has a favorable therapeutic utility against CDDP-induced kidney injury.
Metabolic profiling and gene expression analysis provides insights into flavonoid and anthocyanin metabolism in poplar
Authors: Tian Yuru , Li Qianqian , Rao Shupei , Wang Aike , Zhang Hechen , Wang Liangsheng , Li Yue , Chen Jinhuan
Published: November 2020

Poplar, a woody perennial model, is a common and widespread tree genus. We cultivated two red leaf poplar varieties from bud mutation of Populus sp. Linn. ‘2025’ (also known as Zhonglin 2025, L2025 for shot): Populus deltoides varieties with bright red leaves (LHY) and completely red leaves (QHY). After measuring total contents of flavonoid, anthocyanin, chlorophyll and carotenoid metabolites, a liquid chromatography-electrospray ionization-tandem mass spectrometry system was used for the relative quantification of widely targeted metabolites in leaves of three poplar varieties. A total of 210 flavonoid metabolites (89 flavones, 40 flavonols, 25 flavanones, 18 anthocyanins, 16 isoflavones, 7 dihydroflavonols, 7 chalcones, 5 proanthocyanidins and 3 other flavonoid metabolites) were identified. Compared with L2025, 48 and 8 flavonoids were more and less abundant, respectively, in LHY, whereas 51 and 9 flavonoids were more and less abundant in QHY, respectively. On the basis of a comprehensive analysis of the metabolic network, gene expression levels were analyzed by deep sequencing to screen for potential reference genes for the red leaves. Most phenylpropanoid biosynthesis pathway-involved genes were differentially expressed among the examined varieties. Gene expression analysis also revealed several potential anthocyanin biosynthesis regulators including three MYB genes. The study results provide new insights into poplar flavonoid metabolites and represent the theoretical basis for future studies on leaf coloration in this model tree species.
Antimicrobial susceptibility of bacteria isolated from the infected wounds of patients with lymphoedema in East Wollega, Ethiopia
Authors: Nigussie Dereje , Makonnen Eyasu , Legesse Belete Adefris , Fekadu Abebaw , Davey Gail
Published: November 2020

Background

Lymphoedema is caused by dysfunction of the lymphatic system resulting in accumulation of high-protein content fluid in the interstitial space. To date, the bacteria associated with wound infections of patients with lower limb lymphoedema in Ethiopia have not been studied. This study identified pathogenic bacteria involved in wound infection and assessed antimicrobial susceptibility patterns in patients with lymphoedema in Ethiopia.

Methods

Swab samples were collected from the wounds of patients with lymphoedema and cultured using standard microbiological techniques. Micro-organisms were identified by colony morphology followed by identification and antimicrobial susceptibility testing using the automated VITEK 2 COMPACT Microbial Detection System.

Results

Swabs were collected from 103 patients and 84 were culture positive: 44 (52.4%) culture-positive samples showed polymicrobial growth and 40 (47.6%) grew single bacterial isolates. In total, 134 isolates were obtained, of which 26 gram-negative and 12 gram-positive bacterial species were identified. A total of 28/63 (44.4%) gram-negative isolates and 3/57 (5.3%) gram-positive isolates were multiple drug resistant. There was no resistance to ciprofloxacin, moxifloxacin or gentamycin among gram-negative or gram-positive bacteria.

Conclusion

In this study, many infections were polymicrobial and showed multiple drug resistance. Fluoroquinolones and gentamycin, however, seemed to be effective against bacterial wound infection in this setting.
Complex population structure of the Atlantic puffin revealed by whole genome analyses
Authors: Kersten Oliver , Star Bastiaan , Leigh Deborah M. , Anker-Nilssen Tycho , Strøm Hallvard , Danielsen Jóhannis , Descamps Sébastien , Erikstad Kjell E. , Fitzsimmons Michelle G. , Fort Jérôme , Hansen Erpur S. , Harris Mike P. , Irestedt Martin , Kleven Oddmund , Mallory Mark L. , Jakobsen Kjetill S. , Boessenkool Sanne
Published: November 2020

The factors underlying gene flow and genomic population structure in vagile seabirds are notoriously difficult to understand due to their complex ecology with diverse dispersal barriers and extensive periods at sea. Yet, such understanding is vital for conservation management of seabirds that are globally declining at alarming rates. Here, we elucidate the population structure of the Atlantic puffin (Fratercula arctica) by assembling its reference genome and analyzing genome-wide resequencing data of 72 individuals from 12 colonies. We identify four large, genetically distinct clusters, observe isolation-by-distance between colonies within these clusters, and obtain evidence for a secondary contact zone. These observations disagree with the current taxonomy, and show that a complex set of contemporary biotic factors impede gene flow over different spatial scales. Our results highlight the power of whole genome data to reveal unexpected population structure in vagile marine seabirds and its value for seabird taxonomy, evolution and conservation.
Expectancy-based rhythmic entrainment as continuous Bayesian inference
Authors: Cannon Jonathan
Published: November 2020

When presented with complex rhythmic auditory stimuli, humans are able to track underlying temporal structure (e.g., a “beat”), both covertly and with their movements. This capacity goes far beyond that of a simple entrained oscillator, drawing on contextual and enculturated timing expectations and adjusting rapidly to perturbations in event timing, phase, and tempo. Previous modeling work has described how entrainment to rhythms may be shaped by event timing expectations, but sheds little light on any underlying computational principles that could unify the phenomenon of expectation-based entrainment with other brain processes. Inspired by the predictive processing framework, we propose that the problem of rhythm tracking is naturally characterized as a problem of continuously estimating an underlying phase and tempo based on precise event times and their correspondence to timing expectations. We present two inference problems formalizing this insight: PIPPET (Phase Inference from Point Process Event Timing) and PATIPPET (Phase and Tempo Inference). Variational solutions to these inference problems resemble previous “Dynamic Attending” models of perceptual entrainment, but introduce new terms representing the dynamics of uncertainty and the influence of expectations in the absence of sensory events. These terms allow us to model multiple characteristics of covert and motor human rhythm tracking not addressed by other models, including sensitivity of error corrections to inter-event interval and perceived tempo changes induced by event omissions. We show that positing these novel influences in human entrainment yields a range of testable behavioral predictions. Guided by recent neurophysiological observations, we attempt to align the phase inference framework with a specific brain implementation. We also explore the potential of this normative framework to guide the interpretation of experimental data and serve as building blocks for even richer predictive processing and active inference models of timing.
Identifying latent behavioral states in animal movement with M4, a non-parametric Bayesian method
Authors: Cullen Joshua A , Poli Caroline L , Fletcher Robert J , Valle Denis
Published: November 2020

Understanding animal movement often relies upon telemetry and biologging devices. These data are frequently used to estimate latent behavioral states to help understand why animals move across the landscape. While there are a variety of methods that make behavioral inferences from biotelemetry data, some features of these methods (e.g., analysis of a single data stream, use of parametric distributions) may limit their generality to reliably discriminate among behavioral states.

To address some of the limitations of existing behavioral state estimation models, we introduce a non-parametric Bayesian framework called the mixed-membership method for movement (M4), which is available within the open-sourcebayesmoveR package. This framework can analyze multiple data streams (e.g., step length, turning angle, acceleration) without relying on parametric distributions, which may capture complex behaviors more successfully than current methods. We tested our Bayesian framework using simulated trajectories and compared model performance against two segmentation methods (behavioral change point analysis (BCPA) and segclust2d), one machine learning method (expectation-maximization binary clustering (EMbC)), and one type of state-space model (hidden Markov model (HMM)). We also illustrated this Bayesian framework using movements of juvenile snail kites (Rostrhamus sociabilis) in Florida, USA.

The Bayesian framework estimated breakpoints more accurately than the other segmentation methods for tracks of different lengths. Likewise, the Bayesian framework provided more accurate estimates of behavior than the other state estimation methods when simulations were generated from less frequently considered distributions (e.g., truncated normal, beta, uniform). Three behavioral states were estimated from snail kite movements, which were labeled as ‘encamped’, ‘area-restricted search’, and ‘transit’. Changes in these behaviors over time were associated with known dispersal events from the nest site, as well as movements to and from possible breeding locations.

Our non-parametric Bayesian framework estimated behavioral states with comparable or superior accuracy compared to the other methods when step lengths and turning angles of simulations were generated from less frequently considered distributions. Since the most appropriate parametric distributions may not be obviousa priori, methods (such as M4) that are agnostic to the underlying distributions can provide powerful alternatives to address questions in movement ecology.
Epigenetic dynamics of centromeres and neocentromeres inCryptococcus deuterogattii
Authors: Schotanus Klaas , Yadav Vikas , Heitman Joseph
Published: November 2020

Deletion of native centromeres in the human fungal pathogenCryptococcus deuterogattiileads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To explore the epigenetic organization of neocentromeres, we analyzed the distribution of the heterochromatic histone modification H3K9me2, 5mC DNA methylation and the euchromatin mark H3K4me2. Native centromeres are enriched for both H3K9me2 and 5mC DNA methylation marks and are devoid of H3K4me2, while neocentromeres do not exhibit any of these features. Neocentromeres incen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is inactivated and the native centromere of the chromosome fusion partner remains as the sole, active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted the re-activation of the inactive neocentromere. Our results show that the inactive neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To study the impact of transcription on centromere stability, the actively expressedURA5gene was introduced into the CENP-A bound regions of a native centromere. The introduction of theURA5gene led to a loss of CENP-A from the native centromere, and a neocentromere formed adjacent to the native centromere location. Remarkably, the inactive, native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. A cumulative analysis of multiple CENP-A distribution profiles revealed centromere drift inC. deuterogattii, a previously unreported phenomenon in fungi. The CENP-A-binding shifted within the ORF-free regions and showed a possible association with a truncated transposable element. Taken together, our findings reveal that neocentromeres inC. deuterogattiiare highly unstable and are not marked with an epigenetic memory, distinguishing them from native centromeres.
Modeling CRISPR gene drives for suppression of invasive rodents
Authors: Champer Samuel E. , Oakes Nathan , Sharma Ronin , García-Díaz Pablo , Champer Jackson , Messer Philipp W.
Published: November 2020

Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these new invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse. Such systems might be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit and allows for overlapping generations and a fluctuating population size. Our model includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, but only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning for identifying the key parameters and processes that determine the population dynamics of a complex evolutionary system.
MicroRNA-511-3p mediated modulation of the peroxisome proliferator-activated receptor gamma (PPARγ) controls LPS-induced inflammatory responses in human monocyte derived DCs
Authors: Awuah Dennis , Ruisinger Alisa , Alobaid Meshal , Mbadugha Chidimma , Ghaemmaghami Amir M.
Published: November 2020

The peroxisome proliferator activated receptor gamma (PPARγ) is a ligand activated transcription factor expressed in dendritic cells (DCs), where it exerts anti-inflammatory responses against TLR4-induced inflammation. Recently, microRNA-511 (miR-511) has also emerged as a key player in controlling TLR4-mediated signalling, and in regulating the function of DCs. Interestingly, PPARγ has been previously highlighted as a putative target of miR-511 activity; however the link between miR-511 and PPARγ and its influence on human DC function within the context of LPS-induced inflammatory responses is unknown. Using a selection of miR-511-3p-specific inhibitors and mimics, we demonstrate for the first time that up or downregulation of miR-511-3p inversely correlates with PPARγ mRNA levels and transcriptional activity following treatment with PPARγ synthetic agonist rosiglitazone (RSG), in the presence or absence of LPS. Additionally, we show that PPARγ activation with RSG modulates LPS-induced DC activation and downregulates pro-inflammatory cytokine production following downregulation of miR-511-3p. Lastly, PPARγ activation was shown to suppress LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. These data suggest that PPARγ-induced modulation of DC phenotype and function is influenced by miR-511-3p expression, which may serve as a potential therapeutic target against inflammatory diseases.
Auditory Stimulus-response Modeling with a Match-Mismatch Task
Authors: de Cheveigné Alain , Slaney Malcolm , Fuglsang Søren A. , Hjortkjaer Jens
Published: November 2020

An auditory stimulus can be related to the brain response that it evokes by a stimulus-response model fit to the data. This offers insight into perceptual processes within the brain and is also of potential use for devices such as Brain Computer Interfaces (BCI). The quality of the model can be quantified by measuring the fit with a regression problem, or by applying it to a classification task and measuring its performance. Here we focus on a match-mismatch (MM) task that entails deciding whether a segment of brain signal matches, via a model, the auditory stimulus that evoked it. The MM task allows stimulus-response models to be evaluated in the limit of very high model accuracy, making it an attractive alternative to the more commonly used task of auditory attention detection (AAD). The MM task does not require class labels, so it is immune to mislabeling, and it is applicable to data recorded in listening scenarios with only one sound source, thus it is cheap to obtain large quantities of training and testing data. Performance metrics from this task, associated with regression accuracy, provide complementary insights into the relation between stimulus and response, as well as information about discriminatory power directly applicable to BCI applications. Using these metrics, we describe a range of models of increasing complexity that we compare to methods in the literature, showing state-of-the-art performance. We document in detail one particular implementation, calibrated on a publicly-available database, that can serve as a robust reference to evaluate future developments.
Human visual motion perception shows hallmarks of Bayesian structural inference
Authors: Yang Sichao , Bill Johannes , Drugowitsch Jan , Gershman Samuel J.
Published: November 2020

Motion relations in visual scenes carry an abundance of behaviorally relevant information, but little is known about the computations underlying the identification of visual motion structure by humans. We addressed this gap in two psychophysics experiments and found that participants identified hierarchically organized motion relations in close correspondence with Bayesian structural inference. We demonstrate that, for our tasks, a choice model based on the Bayesian ideal observer can accurately match many facets of human structural inference, including task performance, perceptual error patterns, single-trial responses, participant-specific differences, and subjective decision confidence, particularly when motion scenes are ambiguous. Our work can guide future neuroscience experiments to reveal the neural mechanisms underlying higher-level visual motion perception.