bluuebunny/crossref_metadata_2025 huggingface dataset:
LEA motifs promote desiccation tolerancein vivo
Authors: Hibshman Jonathan D. , Goldstein Bob
Published: February 2021

Background

Cells and organisms typically cannot survive in the absence of water. However, there are some notable exceptions, including animals such as nematodes, tardigrades, rotifers, and some arthropods. One class of proteins known to play a role in desiccation resistance is the late embryogenesis abundant (LEA) proteins. These largely disordered proteins protect plants and animals from desiccation. A multitude of studies have characterized stress-protective capabilities of LEA proteinsin vitroand in heterologous systems. However, the extent to which LEA proteins exhibit such functionsin vivo, in their native contexts in animals, is unclear.

Furthermore, little is known about the distribution of LEA proteins in multicellular organisms or tissue-specific requirements in conferring stress protection.

Results

To study the endogenous function of an LEA protein in an animal, we created a true null mutant ofC. elegansLEA-1, as well as endogenous fluorescent reporters of the protein. We confirmed thatC. eleganslacking LEA-1 are sensitive to desiccation. LEA-1 mutant animals were also sensitive to heat and osmotic stress and were prone to protein aggregation. During desiccation, LEA-1 expression increased and became more widespread throughout the body. LEA-1 was required at high levels in body wall muscle for animals to survive desiccation and osmotic stress. We identified minimal motifs withinC. elegansLEA-1 that are sufficient to increase desiccation survival ofE. coli. To test whether such motifs are central to LEA-1’sin vivofunctions, we then replaced the sequence oflea-1with these minimal motifs and found thatC. eleganssurvived mild desiccation and osmotic stress at the same levels as worms with the full-length protein.

Conclusions

Our results provide insights into the endogenous functions and expression dynamics of an LEA protein in a multicellular animal. The results show that LEA-1 buffers animals from a broad range of stresses. Our identification of LEA motifs that can function in both bacteria and in a multicellular organism suggests the possibility of engineering LEA-1-derived peptides for optimized desiccation protection.
Codon arrangement modulates MHC-I peptides presentation: implications for a SARS-CoV-2 peptide-based vaccine
Authors: Daouda Tariq , Dumont-Lagacé Maude , Feghaly Albert , Villani Alexandra-Chloé
Published: February 2021

Among various vaccination strategies, peptide-based vaccines appear as excellent candidates because they are cheap to produce, are highly stable and harbor low toxicity. However, predicting which MHC-I Associated Peptide (MAP) will ultimately reach cell surface remains challenging, due to high false discovery rates. Previously, we demonstrated that synonymous codon arrangement (usage and placement) is predictive of, and modulates MAP presentation. Here, we apply CAMAP (Codon Arrangement MAP Predictor), the artificial neural network we used to unveil the role of codon arrangement in MAP presentation, to predict SARS-CoV MAPs. We report that experimentally identified SARS-CoV-1 and SARS-CoV-2 MAPs are associated with significantly higher CAMAP scores. Based on CAMAP scores and binding affinity, we identified 48 non-overlapping MAP candidates for a peptide-based vaccine, ensuring coverage for a high proportion of HLA haplotypes in the US population (>78%) and SARS-CoV-2 strains (detected in >98% of SARS-CoV-2 strains present in the GISAID database). Finally, we built an interactive web portal (https://www.epitopes.world) where researchers can freely explore CAMAP predictions for SARS-CoV-1/2 viruses. Collectively, we present an analysis framework that can be generalizable to empower the rapid identification of virus-specific MAPs, including in the context of an emergent virus, to help accelerate target identification for peptide-based vaccine designs that could be critical in safely attaining group immunity in the context of a global pandemic.
Synergistic Cytotoxicity Between Cold Atmospheric Plasma and Pyrazolopyrimidinones Against Glioblastoma Cells
Authors: He Zhonglei , Charleton Clara , Devine Robert , Kelada Mark , Walsh John M.D. , Conway Gillian , Gunes Sebnem , Mondala Julie Rose Mae , Tian Furong , Tiwari Brijesh , Kinsella Gemma K , Malone Renee , O'Shea Denis , Devereux Michael , Wang Wenxin , Cullen Patrick J , Stephens John C. , Curtin James F
Published: February 2021

Pyrazolopyrimidinone is a fused nitrogen-containing heterocyclic system, which acts as a core scaffold in many pharmaceutically relevant compounds. Pyrazolopyrimidinones have been demonstrated to be efficient in treating several diseases, including cystic fibrosis, obesity, viral infection and cancer. We have tested the synergistic anti-cancer effects of 15 pyrazolopyrimidinones, synthesised in a two-step process, combined with cold atmospheric plasma (CAP), a novel innovation generating reactive species with other unique chemical and physical effects. We identify two pyrazolopyrimidinones that act as prodrugs and display enhanced reactive-species dependent cytotoxicity when used in combination with cold atmospheric plasma. Synergistic activation was evident for both direct CAP treatment on prodrug loaded tumour cells and indirect CAP treatment of prodrug in media prior to adding to tumour cells. Our results demonstrate the potential of CAP combined with pyrazolopyrimidinones as a programmable cytotoxic therapy against cancer.
Isogonal piecewise linear embeddings of 1-periodic weaves and some related structures
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: February 2021

Crystallographic descriptions of isogonal piecewise linear embeddings of 1-periodic weaves and links (chains) are presented. These are composed of straight segments (sticks) that meet at corners (2-valent vertices). Descriptions are also given of some plaits – woven periodic bands, three simple periodic knots and isogonal interwoven rods.
A different outlook on othering
Authors: Marques Joan F.
Published: February 2021

Purpose

To encourage those who feel victimized by the tendency of “othering” or being part of an “outgroup” in any organization, in perceiving this reality from a more constructive angle.

Design/methodology/approach

A reflective viewpoint, supported by observations, conversations, and readings.

Findings

Othering exists, but it is a perspective that we can choose as a source of oppression or growth.

Practical implications

Considering the five ideas in this article can assist readers in becoming more resilient and positive members of their work- and other environments.

Social implications

As more people decide to rethink othering, the ridiculousness of the entire tendency may get deposed, and othering may become an obsolete behavioral pattern.

Originality/value

Presenting five ideas pertaining to performance excellence, making a constructive difference, keeping a mindset of elevating rather than defeating perspectives, maintaining dignity, and moving to new horizons. Through these five ideas, the author proposes a constructive perspective to a trend that is usually considered discriminatory and subjugating.
Analysing the AAOIFI Sharīʿah standard on zakat
Authors: Raja Khurram Parvez
Published: February 2021

Purpose

The Sharīʿah Standard No. (35) issued by the Accounting and Auditing Organization for Islamic Financial Institutions (AAOIFI) aims to identify the zakāt base for institutions (including Islamic insurance companies) as well as the subsidiary and the mother company of the institution (the company). By zakāt base, the standard means the items of financial statements that should or should not be included in the calculation of the zakāt base, and the liabilities or allocations that should or should not be deducted from zakatable assets. The standard also covers payable zakāt rates, disbursement of zakāt funds on the eight categories of zakāt recipients and the rulings pertaining to disbursement. The focus then is on companies or corporations. There is no indication in the aims as to who owns the wealth of the corporation, that is, whether it is the company itself or it is the shareholders and whether it is treated as a joint wealth of the shareholders or of a single individual in the form of the company. The author will rely on this issue as one factor on the basis of which the standard is to be judged.

Design/methodology/approach

Quran and hadith. Works of earlier jurists.

Findings

In this study, the author has summarized the provisions of zakāt according to the traditional law, but only those that are relevant for the financial institutions and the standard issued by the AAOIFI. After that, the author mentioned the major points that have been addressed by the standard. In the last section, the author has shown that the rulings of the Islamic Fiqh Academy and the AAOIFI on zakāt are totally confusing and merely a reproduction of the rulings of traditional law. The main reason for this confusion is that the nature and entity of a corporation have not been addressed and have been treated like a partnership, thus, jumbling up the entire issue of zakāt through banks.

Originality/value

The main purpose in undertaking this original work is to examine the AAOIFI Sharīʿah Standards from the perspective of traditional Islamic law, that is, the law of the senior schools as laid down in their authentic manuals. If there is an extensive deviation from this law, then this must be pointed out in the hope that it will be corrected by the concerned institution and the banks that adopt these standards. Neglecting such a corrective action for long will result in damage not only to these institutions in the long run but also to the law of Islam that has been so carefully crafted over centuries. The purpose is to show how far this standard deviates from traditional Islamic law and claims to be called the authentic view on a particular subject. Nevertheless, it is not the purpose of this work to explain and elaborate on the meaning and utility of these standards.
Knowledge Production and Britain's Expansion in China: Constructing the Narrative of the Cruelty of Chinese Punishment in the Nineteenth Century
Authors: YU QIONG
Published: February 2021

This article looks into Britain's knowledge production about China and the Chinese in the nineteenth century, through a case study of how a narrative of the cruelty of Chinese punishment was constructed by publications and activities of two closely connected institutions, the Royal Asiatic Society and the British Consular Service. Concentrating on the period between the end of the First Opium War and the end of the Second Opium War, and looking into the post‐factum criticism, eye‐witness accounts and personal experience of the two institutions, it examines how ideas around the cruelty of Chinese punishment was constructed in relation to Britain's expansion in China, the change of sentiment towards judicial torture in Europe, and the social disorder in South China. Approaching Sino‐British encounters in the nineteenth century from a cultural perspective, this article provides a more comprehensive understanding of British knowledge production of China and the Chinese, and reveals a more complicated picture of Britain's expansion in China, shedding some light on Sino‐British encounters at that time.
Stillbirth: are we making more progress than we think? A retrospective cohort study
Authors: Selvaratnam RJ , Rolnik DL , Davey M‐A , Wallace EM
Published: February 2021

Objective

To quantify how the changing stillbirth risk profile of women is affecting the interpretation of the stillbirth rate.

Design

A retrospective, population‐based cohort study from 1983 to 2018.

Setting

Victoria, Australia.

Population

A total of 2 419 923 births at ≥28 weeks of gestation.

Methods

Changes in maternal characteristics over time were assessed. A multivariable logistic regression model was developed for stillbirth, based on maternal characteristics in 1983–1987, and used to calculate individual predictive probabilities of stillbirth from the regression equation. The number of expected stillbirths per year as a result of the change in maternal demographics was then calculated, assuming no changes in care and in the associations between maternal characteristics and stillbirth over time.

Main outcome measure

Stillbirth.

Results

Compared with 1983–1987, there were more women in older age groups giving birth, more nulliparous women, more indigenous women and women born in Oceania, Asia and Africa, more multiple pregnancies and more women with pre‐existing diabetes in 2014–2018. Despite this, the rate of stillbirth fell from 5.42 per 1000 births in 1983 to 1.72 per 1000 births in 2018 (P < 0.001). Applying the multivariable logistic regression equation, derived from the 1983–87 data, to each year, had there been no changes in care or in the associations between maternal characteristics and stillbirth, the rate of stillbirth would have increased by 12%, from 4.94 per 1000 in 1983 to 5.54 per 1000 in 2018, as a result of the change in maternal characteristics.

Conclusions

Population rates of stillbirth are falling faster than is generally appreciated.

Tweetable abstract

Population reductions in stillbirth have been underestimated as a result of changing maternal characteristics.
Distribution of semen examination results 2020 – A follow up of data collated for the WHO semen analysis manual 2010
Authors: Campbell Martin J. , Lotti Francesco , Baldi Elisabetta , Schlatt Stefan , Festin Mario P. R. , Björndahl Lars , Toskin Igor , Barratt Christopher L. R.
Published: February 2021

Background

It is now 11 years since publication of the WHO 2010 guidelines for semen assessment values, and it is critical to determine whether they are still valid and/or whether they should be modified.

Objectives

To utilise data published since 2010 and combine these with data used in the 2010 assessment to provide an updated and more comprehensive representation of the fertile man. This may be utilised to present an updated distribution of values for use by WHO in 2021.

Materials and Methods

Two specific analyses were performed namely, (1) Analysis 1: Examination of published data following publication of WHO 2010 [termed 2010–2020 data]. (2) Analysis 2: Examination of the data used to help formulate the 2010 distribution of values combined with the data from Analysis (1) [termed WHO 2020].

Results

In total, data from more than 3500 subjects, from twelve countries and five continents were analysed. The 5th centile values for concentration, motility and morphology are: 16 × 106/ml, 30% progressive motility [42% total motility] and 4% normal forms.

Discussion

This study presents substantial additional information to establish more comprehensive and globally applicable lower reference values for semen parameters for fertile men although they do not represent distinct limits between fertile and subfertile men. There are still data missing from many countries and, some geographical regions are not represented. Moreover, the number of subjects although significant is still relatively low (<4000).

Conclusion

These distributions of values now include semen analysis providing a more global representation of the fertile man. Increasing the number of subjects provides robust information that is also more geographically representative.
Developing a physiologically based pharmacokinetic model of apixaban to predict scenarios of drug–drug interactions, renal impairment and paediatric populations
Authors: Xu Ruijuan , Tang Hong , Chen Lin , Ge Weihong , Yang Jin
Published: February 2021

Aims

To develop a physiologically based pharmacokinetic (PBPK) model for apixaban, an oral anticoagulant with a narrow therapeutic index, and to predict PK profiles and potential drug–drug interactions (DDIs) in patients with renal impairment and paediatrics.

Methods

A whole‐body apixaban PBPK model was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extended to renal impairment and paediatrics. Observed PK data in adults were compared with predicted data. The effect of renal function, age and DDIs on apixaban PK was investigated.

Results

The PBPK model successfully predicted the PK of apixaban alone and under the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group; inhibitory DDI and renal impairment had a synergistic effect on the increase of apixaban exposure (e.g., almost 3‐fold increase of AUC in ketoconazole + severe renal impairment group). For infants younger than 1 year, the exposure of apixaban decreased with increased weight‐normalized clearance. For newborn infants, AUC of apixaban was >2‐fold higher than that in children older than 1 year. Meanwhile, the effect of DDI seems to be weakened while the effect of renal impairment might be enhanced in infants younger than 1 year.

Conclusion

Our study provides a reasonable approach to estimate the dose adjustment for the first use of apixaban in special populations with complex situations, which has the opportunity to make the clinical practice much safer.
Synthesizing external aggregated information in the presence of population heterogeneity: A penalized empirical likelihood approach
Authors: Sheng Ying , Sun Yifei , Huang Chiung‐Yu , Kim Mi‐Ok
Published: February 2021

With the increasing availability of data in the public domain, there has been a growing interest in exploiting information from external sources to improve the analysis of smaller scale studies. An emerging challenge in the era of big data is that the subject‐level data are high dimensional, but the external information is at an aggregate level and of a lower dimension. Moreover, heterogeneity and uncertainty in the auxiliary information are often not accounted for in information synthesis. In this paper, we propose a unified framework to summarize various forms of aggregated information via estimating equations and develop a penalized empirical likelihood approach to incorporate such information in logistic regression. When the homogeneity assumption is violated, we extend the method to account for population heterogeneity among different sources of information. When the uncertainty in the external information is not negligible, we propose a variance estimator adjusting for the uncertainty. The proposed estimators are asymptotically more efficient than the conventional penalized maximum likelihood estimator and enjoy the oracle property even with a diverging number of predictors. Simulation studies show that the proposed approaches yield higher accuracy in variable selection compared with competitors. We illustrate the proposed methodologies with a pediatric kidney transplant study.
Peptide allergen‐specific immunotherapy for allergic airway diseases—State of the art
Authors: Wraith David C. , Krishna Mamidipudi T.
Published: February 2021

Allergen‐specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long‐term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side‐effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.
Transanal opening of the intersphincteric space: a novel sphincter‐sparing procedure to treat 325 high complex anal fistulas with long‐term follow‐up
Authors: Garg Pankaj , Kaur Baljit , Menon Geetha R.
Published: February 2021

Aim

Sepsis in the intersphincteric plane behaves like an abscess in a closed space and is present in most complex fistulas. Ignoring this sepsis is a cause of recurrence. Complex fistulas can be successfully managed by transanal opening of the intersphincteric space (TROPIS) into the anal canal. The long‐term efficacy of the TROPIS procedure was analysed in an exclusive cohort of high complex anal fistulas.

Methods

All consecutive patients operated for a high complex fistula‐in‐ano were included prospectively. Preoperative MRI scans were obtained for all the patients. The intersphincteric space and internal opening was laid open into the anal canal while preserving the external sphincter. The external tracts were thoroughly curetted and cleaned. Fistula healing rate and objective incontinence scores (preoperatively and during long‐term follow‐up) were analysed.

Results

A total of 325 patients (age 39.9 ± 10.9 years, 292 men) were operated with TROPIS and had a follow‐up of 7–67 months (median 36 months). In the cohort, 67.4% (219) had recurrent fistulas, 82.8% (269) had multiple tracts, 36.3% (118) had horseshoe tracts, 37.5% (122) had associated abscesses and 24% (78) were supralevator fistulas. Nineteen patients were excluded. Fistulas healed completely in 78.4% (240/306) of patients and did not heal in 21.6% (66/306) of patients. 36/66 of these patients were operated again and the fistulas healed in 28 patients. Thus, the overall healing rate was 87.6% (268/306). The mean preoperative and postoperative incontinence scores were 0.085 ± 0.35 and 0.119 ± 0.48 respectively (P = 0.38). The healing rate of fistulas with associated acute abscesses was similar to the fistulas without abscesses (87% vs. 88%, P = 0.85).

Conclusion

Transanal opening of the intersphincteric space is a safe and highly effective sphincter‐sparing procedure to manage high complex fistulas‐in‐ano.
Development of directed and random exploration in children
Authors: Meder Björn , Wu Charley M. , Schulz Eric , Ruggeri Azzurra
Published: February 2021

Are young children just random explorers who learn serendipitously? Or are even young children guided by uncertainty‐directed sampling, seeking to explore in a systematic fashion? We study how children between the ages of 4 and 9 search in an explore–exploit task with spatially correlated rewards, where exhaustive exploration is infeasible and not all options can be experienced. By combining behavioral data with a computational model that decomposes search into similarity‐based generalization, uncertainty‐directed exploration, and random exploration, we map out developmental trajectories of generalization and exploration. The behavioral data show strong developmental differences in children's capability to exploit environmental structure, with performance and adaptiveness of sampling decisions increasing with age. Through model‐based analyses, we disentangle different forms of exploration, finding signature of both uncertainty‐directed and random exploration. The amount of random exploration strongly decreases as children get older, supporting the notion of a developmental “cooling off” process that modulates the randomness in sampling. However, even at the youngest age range, children do not solely rely on random exploration. Even as random exploration begins to taper off, children are actively seeking out options with high uncertainty in a goal‐directed fashion, and using inductive inferences to generalize their experience to novel options. Our findings provide critical insights into the behavioral and computational principles underlying the developmental trajectory of learning and exploration.
Hitler's theology: A cautionary tale for today's peril
Authors: Hinlicky Paul R.
Published: February 2021

In this article the author updates and renews his thesis from 2013 about the Weimarization of American political culture. He argues that fascism is an endemic modern possibility that has a theological dimension that becomes visible when the left‐right ideological binary descending from the French Revolution is set aside. Reviewing the evidence from Hitler's Table Talks, he shows how Hitler both understood himself as a progressive change agent and envisioned writing a new theology for triumphant Nazism in retirement. The article concludes by drawing upon Giorgio Agamben's analysis of Nazi biopolitics in Homo Sacer to point towards a messianic alternative.
Covid‐19's impact on China's economy: a prediction model based on railway transportation statistics
Authors: Wang Yunhao , Fang Zhiqiang , Gao Wei
Published: February 2021

The outbreak of Covid‐19 in China during the Spring Festival of 2020 has changed life as we knew it. To explore its impact on China's economy, we analyse the daily railway passenger volume data during the Spring Festival travel rush and establish two RegARMA models to predict GDP in the first quarter. The models forecast China might lose 4.8 trillion yuan in the first quarter of 2020 due to Covid‐19, an expected decrease of 20.69 percent (year‐on‐year drop 15.60 percent). However, comparing our forecast GDP without Covid‐19 (23.2 trillion yuan) with the real GDP (20.65 trillion yuan), there is a smaller drop of 2.55 trillion yuan, a gap of 12.35 percent. The reason for this overestimation is that some positive factors, including macro‐control policies, are neglected in these models. With the global spread of Covid‐19, China should adopt a policy of focusing on balancing both domestic and external affairs against the instability of the world economy.
Attracting altruists: explaining volunteer turnout during natural hazard events in Japan
Authors: Iizuka Akiko , Aldrich Daniel P.
Published: February 2021

Volunteers play a crucial role in post‐disaster situations, providing resources, emotional support, and labour when local and national government capacity may be diminished. The number of volunteers who assist can range from dozens to more than one million. Yet, little is known about the broader conditions that result in more (or fewer) of them heading to disaster sites. Using a new dataset of 57 disasters in Japan between 1995 and 2019, this study analyses the factors influencing volunteer turnout. Controlling for a number of aspects, three are found to correlate most strongly: the number of dead and missing; the size of the population affected by the shock; and the time period of the year. Moving beyond tables of regression coefficients, simulations and graphics are used to illustrate the relationship between key variables of interest as well as uncertainty about the predictions. The study's findings—robust across multiple model types—have important policy and practical implications.
The effects of hydroxychloroquine on insulin sensitivity, insulin clearance and inflammation in insulin‐resistant adults: A randomized trial
Authors: Toledo Frederico G. S. , Miller Rachel G. , Helbling Nicole L. , Zhang Yingze , DeLany James P.
Published: February 2021

Aim

To determine the effect of hydroxychloroquine (HCQ) on skeletal muscle and liver insulin sensitivity, insulin clearance, inflammation and adipokines.

Methods

Insulin‐resistant adults without rheumatic disease were randomized to 13 weeks of HCQ (400 mg/day) versus placebo (double‐blinded). Primary outcomes were changes in skeletal muscle and liver insulin sensitivity assessed by hyperinsulinaemic‐euglycaemic clamp and stable‐isotope tracer methods. Secondary outcomes included insulin clearance, inflammation biomarkers and adipokines.

Results

Compared with placebo, HCQ significantly improved skeletal muscle insulin sensitivity by 26% (p = .019) and enhanced systemic glucose clearance (p = .025). By contrast, HCQ had no effect on hepatic insulin sensitivity. HCQ did not affect insulin clearance but decreased circulating IL‐6 (p = .01) and increased adiponectin (p = .045). There were no effects on leptin, RBP‐4, FGF‐21 or C‐reactive protein.

Conclusions

HCQ selectively enhances insulin sensitivity and glucose disposal in skeletal muscle, without affecting hepatic insulin sensitivity or insulin clearance. These findings offer a mechanistic explanation for the antidiabetic properties of HCQ and suggest that this medication might be useful in conditions linked to insulin resistance such as type 2 diabetes.
Pre‐stimulus alpha‐band power and phase fluctuations originate from different neural sources and exert distinct impact on stimulus‐evoked responses
Authors: Zazio Agnese , Ruhnau Philipp , Weisz Nathan , Wutz Andreas
Published: February 2021

Ongoing oscillatory neural activity before stimulus onset influences subsequent visual perception. Specifically, both the power and the phase of oscillations in the alpha‐frequency band (9–13 Hz) have been reported to predict the detection of visual stimuli. Up to now, the functional mechanisms underlying pre‐stimulus power and phase effects on upcoming visual percepts are debated. Here, we used magnetoencephalography recordings together with a near‐threshold visual detection task to investigate the neural generators of pre‐stimulus power and phase and their impact on subsequent visual‐evoked responses. Pre‐stimulus alpha‐band power and phase opposition effects were found consistent with previous reports. Source localization suggested clearly distinct neural generators for these pre‐stimulus effects: Power effects were mainly found in occipital‐temporal regions, whereas phase effects also involved prefrontal areas. In order to be functionally relevant, the pre‐stimulus correlates should influence post‐stimulus processing. Using a trial‐sorting approach, we observed that only pre‐stimulus power modulated the Hits versus Misses difference in the evoked response, a well‐established post‐stimulus neural correlate of near‐threshold perception, such that trials with stronger pre‐stimulus power effect showed greater post‐stimulus difference. By contrast, no influence of pre‐stimulus phase effects were found. In sum, our study shows distinct generators for two pre‐stimulus neural patterns predicting visual perception, and that only alpha power impacts the post‐stimulus correlate of conscious access. This underlines the functional relevance of prestimulus alpha power on perceptual awareness, while questioning the role of alpha phase.
Inferring translational heterogeneity from Saccharomyces cerevisiae ribosome profiling
Authors: do Couto Bordignon Pedro , Pechmann Sebastian
Published: February 2021

Translation of mRNAs into proteins by the ribosome is the most important step of protein biosynthesis. Accordingly, translation is tightly controlled and heavily regulated to maintain cellular homeostasis. Ribosome profiling (Ribo‐seq) has revolutionized the study of translation by revealing many of its underlying mechanisms. However, equally many aspects of translation remain mysterious, in part also due to persisting challenges in the interpretation of data obtained from Ribo‐seq experiments. Here, we show that some of the variability observed in Ribo‐seq data has biological origins and reflects programmed heterogeneity of translation. Through a comparative analysis of Ribo‐seq data from Saccharomyces cerevisiae, we systematically identify short 3‐codon sequences that are differentially translated (DT) across mRNAs, that is, identical sequences that are translated sometimes fast and sometimes slowly beyond what can be attributed to variability between experiments. Remarkably, the thus identified DT sequences link to mechanisms known to regulate translation elongation and are enriched in genes important for protein and organelle biosynthesis. Our results thus highlight examples of translational heterogeneity that are encoded in the genomic sequences and tuned to optimizing cellular homeostasis. More generally, our work highlights the power of Ribo‐seq to understand the complexities of translation regulation.
Inactive and inefficient: Warming and drought effect on microbial carbon processing in alpine grassland at depth
Authors: Zhu Erxiong , Cao Zhenjiao , Jia Juan , Liu Chengzhu , Zhang Zhenhua , Wang Hao , Dai Guohua , He Jin‐Sheng , Feng Xiaojuan
Published: February 2021

Subsoils contain >50% of soil organic carbon (SOC) globally yet remain under‐investigated in terms of their response to climate changes. Recent evidence suggests that warmer, drier conditions in alpine grasslands induce divergent responses in SOC decomposition and carbon accrual in top‐ versus subsoils. However, longer term effects on microbial activity (i.e., catabolic respiration vs. anabolic growth) and belowground carbon cycling are not well understood. Here we utilized a field manipulation experiment on the Qinghai‐Tibetan Plateau and conducted a 110‐day soil incubation with and without 13C‐labeled grass litter to assess microbes' role as both SOC “decomposers” and “contributors” in the top‐ (0–10 cm) versus subsoils (30−40 cm) after 5 years of warming and drought treatments. Microbial mineralization of both SOC and added litter was examined in tandem with potential extracellular enzyme activities, while microbial biomass synthesis and necromass accumulation were analyzed using phospholipid fatty acids and amino sugars coupled with 13C analysis, respectively. We found that warming and, to a lesser extent, drought decreased the ratio of inorganic nitrogen (N) to water‐extractable organic carbon in the subsoil, intensifying N limitation at depth. Both SOC and litter mineralization were reduced in the subsoil, which may also be related to N limitation, as evidenced by lower hydrolase activity (especially leucine aminopeptidase) and reduced microbial efficiency (lower biomass synthesis and necromass accumulation relative to respiration). However, none of these effects were observed in the topsoil, suggesting that soil microbes became inactive and inefficient in subsoil but not topsoil environments. Given increasing belowground productivity in this alpine grassland under warming, both elevated root deposits and diminished microbial activity may contribute to new carbon accrual in the subsoil. However, the sustainability of plant growth and persistence of subsoil SOC pools deserve further investigation in the long term, given the aggravated N limitation at depth.
Quick validation of genetic quality for conditional alleles in mice
Authors: Nakata Hatsumi , Hashimoto Tomomi , Yoshiki Atsushi
Published: February 2021

Site‐specific conditional inactivation technologies using Cre‐loxP or Flp‐FRT systems are becoming increasingly important for the elucidation of gene function and disease mechanism in vivo. A large number of gene knockout mouse models carrying complex conditional alleles have been generated by global community efforts and made available for biomedical researchers. The structures of conditional alleles in these mice are becoming increasingly complex and sophisticated, and so the validation of the genetic quality of these alleles is likewise becoming a laborious task for individual researchers. To ensure the reproducibility of conditional experiments, the researcher should confirm that loxP or FRT is integrated at the correct positions in the genome prior to start of the experiments. We report the successful design of universal PCR primers specific to loxP and FRT for the quick validation of conditional floxed and Flrted alleles. The primer set consists of forward and reverse primers complimentary to the loxP or FRT sequences with partial modifications at the 5ʹ end containing 6‐base restriction endonuclease recognition sites. The universal primer set was tested to detect genomic intervals between a pair of cis‐integrated loxP or FRT and was useful for quickly validating various floxed or Flrted alleles in conditional mice.
Rethinking gender equity in the contaminated university: A methodology for listening for music in the ruins
Authors: Locke Kirsten , Lund Rebecca W. B. , Wright Susan
Published: February 2021

This paper offers a new way to engage with gender, race, and class relations in academic leadership and organizations. Viewing our research materials through different images helps us to ask new questions, open up new kinds of answers and ultimately other ways of knowing gender and leadership in academia. Our approach has three connected steps. Firstly, we engage with the ruins of the three main promises upon which the contemporary university has been built: enlightenment, liberalism, and feminism, drawing on Anna Tsing's mushrooms at the end of the world and Gibson‐Graham's notion of a post‐capitalist economy. Secondly, we use intersectionality as a methodological lens, combining it with Karen Barad's ideas about how “matter comes to matter.” We explore the intersections between four themes arising from the accounts of our participants: Reshaping the disciplinary field; gender, class, and race; traveling and mobility; and Institutional structures and policies. The third and final step engages with how some women successfully coordinate these intersecting themes to navigate their careers and achieve leadership positions within the contaminated and ruinous university environment. In doing so, we draw on the musical form of the fugue with its four themes that at different moments diverge, clash and, if successful, achieve resolution, to provide us with a way for analyzing the women's stories as “polyphony‐in‐action.” By using this musical approach to retool intersectionality, we are able to show how some women managed to bring all four themes of their lives into symbiosis and achieve value in the ruinous academic landscape.
In situ investigation of tensile behavior of Cf/SiC mini composites
Authors: Chen Xihui , Sun Zhigang , Niu Xuming , Song Yingdong
Published: February 2021

This study presents an in depth analysis over the in situ tensile behavior of Cf/SiC mini composites. As part of the process, the matrix crack spacing at saturation was determined by the in situ x‐ray microtomography tensile test and the test results were compared with others obtained by in situ optical microscope tensile test and scanning electron microscopy scan. Moreover, elastic modulus of fiber and matrix as well as interface shear stress were identified by the indirect method and in situ modulus of C fibers and SiC matrix were also measured by the nanoindentation test, showing outcomes much lower than those identified by indirect method. The in situ property parameters measured by in situ XCT tensile test and identified by the indirect method were substituted into the shear‐lag model to predict the stress‐strain responses of Cf/SiC mini composites and the predicted results agrees well with the experimental data, while there exists large deviation between the stress‐strain response predicted by using the in situ modulus of C fibers tested by nanoindentation and the experimental data, which indicates that in situ modulus of C fibers tested by nanoindentation tests cannot be utilized to model the tensile stress‐strain responses due to the possible asymmetry of tension and compression of C fibers.
Efficacy of different platelet‐rich plasma injections in the treatment of mild‐moderate knee osteoarthritis: A systematic review and meta‐analysis
Authors: Chou Shih‐Hsiang , Shih Chia‐Lung
Published: February 2021

Aims

This study aimed to compare the efficacy of different numbered sets of injections of platelet‐rich plasma (PRP) in the treatment of mild‐moderate knee osteoarthritis (OA).

Methods

A comprehensive search in three databases of Cochrane Library, Embase, and PubMed was conducted to find relevant articles that investigated the efficacy of PRP injection therapies in the treatment of mild‐moderate knee OA through August 2020. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were the primary outcomes and visual analogue scale (VAS) was the secondary outcome. The pooled improvements amongst different injection therapies were compared.

Results

No significant differences in the improvement of WOMAC pain were observed amongst 1‐, 2‐, and 3‐injection therapies at 3‐ (P = .26) and 6‐month (P = .13) follow‐ups. For a 12‐month follow‐up, the difference amongst different therapies reached borderline significance (P = .05) in which 3‐injection therapy had a significantly better improvement than 2‐injection therapy (P = .02) and reached borderline significance compared with 1‐injection (P = .07). However, no significant differences in the improvement of VAS scores were observed amongst three injection therapies for all the follow‐up visits (P > .05). For WOMAC function score, 3‐injection therapy performed significantly better than 1‐injection (P < .00001) or 2‐injection therapy (P < .0001) only at 12‐month follow‐up visit.

Conclusions

Our results demonstrated that 3‐injection therapy of PRP in the treatment of mild‐moderate knee OA had the best efficacy in pain relief and function improvement compared with 1‐ and 2‐injection therapies.
Comparing the views of the Italian general public and scientists on GMOs
Authors: Pappalardo Gioacchino , D’Amico Mario , Lusk Jayson L.
Published: February 2021

The gap between statements from scientific organisations about the safety of genetically modified (or GMO) food and public concerns about the technology is puzzling, raising questions about the extent to which expert opinion and scientific consensus can sway public opinion and whether scientific progress might be hindered by public opposition. This study sought to determine whether beliefs about GMO safety are high among experts in countries where there has been significant public opposition to the technology. Surveys conducted among 1006 members of the Italian general public and 258 members of the Italian Association of the Agricultural Science Societies (AISSA) reveal that whereas 54% of our sample of the Italian general public believes GMOs are generally safe to eat, 81% of sample of the Italian agricultural scientists believe the same. Despite the gap in lay‐expert safety beliefs, results reveal greater similarity between scientists and the general public on topics related to beliefs about the impact of GM food on food prices, the developing world and concentration in the agricultural supply chain.
Flapless application of enamel matrix derivative in periodontal retreatment: A multicentre randomized feasibility trial
Authors: Jentsch Holger F. R. , Roccuzzo Mario , Pilloni Andrea , Kasaj Adrian , Fimmers Rolf , Jepsen Søren
Published: February 2021

Aim

To investigate the potential benefit of enamel matrix derivative (EMD) as adjunct to re‐instrumentation of residual pockets persisting after steps 1 and 2 of periodontal therapy.

Material and Methods

44 adult patients participated in a multicentre feasibility randomized clinical trial with split‐mouth design. They had presented at re‐evaluation after initial non‐surgical periodontal therapy (steps 1 and 2 of periodontal therapy) for generalized periodontitis with at least 2 teeth with residual probing pocket depths (PPD) ≥5 and ≤8 mm, with bleeding on probing (BOP). Two teeth with similar PPD were randomized to receive re‐instrumentation either with (test) or without (control) adjunctive flapless administration of EMD. Differences in the changes of PPD and BOP from baseline to 6 and 12 months were analysed, and the frequencies of pocket closure (PPD ≤4 mm and no BOP) compared.

Results

For the primary outcome “change of mean PPD after 6 months,” a significant additional benefit of 0.79 ± 1.3 mm (p < .0001) could be observed for the test group. At 12 months, this difference could be maintained (0.85 ± 1.1 mm; p < .0001). The frequency of pocket closure in the test group was 69% at 6 and 80% at 12 months and significantly higher than in the control group with 34% and 42%, respectively (p < .01).

Conclusions

The results of the present feasibility study indicate a benefit of adjunctive EMD during non‐surgical retreatment (step 3 of periodontal therapy) of residual deep pockets.
Maternal effects shape offspring physiological condition but do not senesce in a wild mammal
Authors: Cheynel Louise , Gilot‐Fromont Emmanuelle , Rey Benjamin , Quéméré Erwan , Débias François , Duhayer Jeanne , Pardonnet Sylvia , Pellerin Maryline , Gaillard Jean‐Michel , Lemaître Jean‐François
Published: February 2021

In vertebrates, offspring survival often decreases with increasing maternal age. While many studies have reported a decline in fitness‐related traits of offspring with increasing maternal age, the study of senescence in maternal effect through age‐specific changes in offspring physiological condition is still at its infancy. We assessed the influence of maternal age and body mass on offspring physiological condition in two populations of roe deer (Capreolus capreolus) subjected to markedly different environmental conditions. We measured seven markers to index body condition and characterize the immune profile in 86 fawns which became recently independent of their known‐aged mothers. We did not find striking effects of maternal age on offspring physiological condition measured at 8 months of age. This absence of evidence for senescence in maternal effects is likely due to the strong viability selection observed in the very first months of life in this species. Offspring physiological condition was, on the other hand, positively influenced by maternal body mass. Between‐population differences in environmental conditions experienced by fawns also influenced their average body condition and immune phenotype. Fawns facing food limitation displayed lower values in some markers of body condition (body mass and haemoglobin levels) than those living in good quality habitat. They also allocated preferentially to humoral immunity, contrary to those living in good conditions, which allocated more to cellular response. These results shed a new light on the eco‐physiological pathways mediating the relationship between mother's mass and offspring condition.
Intense pulsed light versus cryotherapy in the treatment of hypertrophic scars: A clinical and histopathological study
Authors: Salem Samar A.M. , Abdel Hameed Sharief M. , Mostafa Azza E.
Published: February 2021

Background

Different therapeutic modalities have been tried for hypertrophic scar treatment. To our knowledge, intense pulsed light (IPL) has not been previously evaluated in comparison with cryotherapy as a stand‐alone treatment for hypertrophic scars.

Objective

We aimed to evaluate the efficacy of IPL as a monotherapy for hypertrophic scar treatment as compared with cryotherapy both clinically and histopathologically.

Methods

This study included 28 patients with hypertrophic scars. Patients were divided randomly and equally into two groups; group I patients received cryotherapy while group II patients received IPL. All patients received treatments for a total of six sessions or until resolution of the lesion whichever was nearer. The outcome was evaluated clinically and histopathologically.

Results

Scar height showed a significant decrease and scar color and pliability showed a significant improvement in group I. No significant changes were detected in group II except in scar pliability. Vancouver scar scale (VSS) mean decreased by −53.7% in group I versus −11.5% decrease in group II. Histopathologically, group I showed a significantly increased epidermal thickness and decreased dermal and collagen bundle thickness, while group II showed insignificant histopathological changes. Group I exhibited a statistically significant clinical and histopathological improvement compared to group II, yet with more complications.

Conclusion

Cryotherapy is more effective than IPL in the treatment of hypertrophic scars both on clinical and histopathological level yet with more complications.