bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Operative Competency in Cochlear Implantation Across the Residency Training Continuum
Authors: Dowling Eric M. , Carlson Matthew L.
Published: December 2020

Objective:

To derive normative data based on postgraduate year (PGY) and number of completed otology rotations using a validated tool for cochlear implant surgical competency assessment.

Study Design:

Prospective, blinded validation study.

Setting:

Otolaryngology–Head and Neck Surgery residency training program at a tertiary academic medical center.

Patients:

Fourteen unique otolaryngology trainees, ranging from PGY-1 to PGY-6, were assessed a total of 26 times in a temporal bone laboratory setting using a validated assessment tool for cochlear implantation.

Main Outcome Measures:

Construct validity, internal consistency, and inter-rater reliability.

Results:

Inter-rater reliability was calculated using the Cohen's kappa. Overall agreement between raters was excellent (κ = 0.82). Construct validity was supported by a positive association between higher task-based checklist and global rating scale scores with both trainee PGY level and number of otology rotations completed. Time to complete the exercise was inversely associated with PGY level and number of otology rotations completed.

Conclusion:

Herein, we build upon a previously validated instrument to provide a method to reliably assess surgical competency in a core otologic procedure among residents across the training continuum. This data can be used to provide objective feedback on overall and task-specific competency in cochlear implantation to identify surgical deficiencies early on and to guide supportive course correction.
Classification of the Chorda Tympani: An Endoscopic Study
Authors: Uranaka Tsukasa , Matsumoto Yu , Hoshi Yujiro , Iwasaki Shinichi , Kakigi Akinobu , Yamasoba Tatsuya
Published: December 2020

Objectives:

To determine the ability of preoperative computed tomography (CT) to predict the variable surgical anatomy of the chorda tympani nerve (CTN) based on endoscopic tympanotomy.

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

We identified 192 ears of 162 patients who underwent transcanal endoscopic ear surgery from August 2013 to June 2018. Patients with middle ear malformations, revision surgeries, myringoplasty, and cholesteatoma involving the CTN were excluded.

Intervention(s):

An intraoperative endoscopic image depicting the chorda tympani was selected for each patient and classified into one of five types. Preoperative CT images were analyzed to match the pictorial classification.

Main Outcome Measure(s):

The visible tympanic segment of the chorda tympani was classified into the following five types: external auditory canal (EAC), detached, attached long, attached short, and ultrashort.

Results:

A total of 128 ears from 101 patients ranging in age from 2 to 81 years were enrolled. The EAC, detached, attached long, attached short, and ultrashort types of CTN were found in 7 (5.5%), 6 (4.7%), 84 (65.6%), 18 (14.0%), and 13 (10.2%) patients, respectively. The presence of the EAC type could be predicted by preoperative CT while the other four types could be predicted by binning into two groups, with a sensitivity of 0.61 and specificity of 0.72.

Conclusion:

The variable anatomy of the chorda tympani nerve can be classified into five major groups based on endoscopic tympanotomy.
Sexually Transmitted Infection/HIV Testing Among Medicaid/Children’s Health Insurance Program–Insured Enrollees Aged 15 to 60 Years Who Were Diagnosed With High-Risk Sexual Behaviors With Their Opposite-Sex or Same-Sex Partners
Authors: Tao Guoyu , Patel Chirag
Published: December 2020

Background

There is a lack of information on high-risk sexual behaviors (HRSB) related to gender of sex partner and associated sexually transmitted infection (STI)/HIV testing among Medicaid enrollees.

Methods

We used the 2016 Centers for Medicare & Medicaid Services Medicaid claims data to identify enrollees aged 15 to 60 years with HRSB by International Classification of Disease, Tenth Revision codes (Z72.51, Z72.52, and Z72.53). Enrollees diagnosed with HRSB were classified into 2 groups:(1) with same-sex partners and (2) with opposite-sex partners. The date when the initial diagnosis for HRSB was documented was used to define as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing on the index date, in the 6-month period before and after the index date (excluded the index date). HIV testing was limited to enrollees without documented HIV infection.

Results

Of 50 million Medicaid enrollees aged 15 to 60 years, 1.2% were identified as enrollees with HRSB in 2016. Of those enrollees with HRSB, 2.7% were enrollees with same-sex partners and 0.71% had documented HIV infection. Chlamydia, gonorrhea, syphilis, and HIV testing rates were 82.4%, 81.9%, 33.2%, and 44.3%, respectively, at the index date. The chlamydia testing rate was ≥90% among enrollees who resided in the West compared with 53% to 61% across other regions. HIV testing was more likely among males and among those with same-sex partners. Sexually transmitted infection/HIV testing was <30% in the 6-month periods before and after the index date.

Conclusions

Among Medicaid enrollees with HRSB, STI/HIV testing varied regionally. Many enrollees were not tested for STI/HIV at the index visit in which they were identified as HRSB.
Variables Associated With Perceived Risk of Contracting SARS-CoV-2 Infection During the COVID-19 Pandemic Among Patients With Systemic Rheumatic Diseases
Authors: Duculan Roland , Jannat-Khah Deanna , Mehta Bella , Mandl Lisa A. , Barbhaiya Medha , Bass Anne R. , Mancuso Carol A.
Published: December 2020

Objective

The aim of this study was to assess patients' perceived risk of contracting SARS-CoV-2 at the peak of the pandemic in NYC in terms of their systemic rheumatic disease and medications.

Methods

With the approval of their rheumatologists, patients were interviewed by telephone and were asked about their perceived risk of contracting SARS-CoV-2 considering their rheumatic condition and whether medications increased this risk. Patients also completed surveys assessing beliefs about medication and multidimensions of physical/mental well-being. Information about current medications and rheumatologist-initiated changes in medications during the pandemic were reported by patients and verified from medical records.

Results

One hundred twelve patients (86% women; mean age, 50 years; 81% White, 15% Latino) with diverse diagnoses were enrolled. Fifty-four percent thought they were at “very much greater risk” of COVID-19 because of their rheumatic condition, and 57% thought medications “definitely” put them at greater risk. In multivariable analysis, the perception of “very much greater risk” was associated with greater belief that rheumatic disease medications were necessary, worse physical function, chronic pulmonary comorbidity, and more anxiety. In a separate model, the perception that medications “definitely” caused greater risk was associated with White race, not taking hydroxychloroquine, rheumatologists initiating change in medications, more anxiety, and taking biologics and corticosteroids.

Conclusions

Patients’ perceived increased risk of contracting SARS-CoV-2 was associated with beliefs about their rheumatic disease, medications, comorbidity, and anxiety. Clinicians should be aware of patients’ perceptions and foster self-management practices that will alleviate anxiety, minimize exposure to the virus, and optimize systemic rheumatic disease outcomes.
Scooping Rice Into a Glass and Putting a Cell Phone in the Refrigerator: Action Slips in an Individual With a Diffuse Axonal Injury
Authors: Nakajima Asuka , Funayama Michitaka , Nakamura Tomoyuki
Published: December 2020

A 39-year-old man with a diffuse axonal injury self-presented to the cognitive function clinic of the Ashikaga Red Cross Hospital complaining of behavioral errors in his daily life, such as scooping hot rice into a glass instead of a bowl or forgetting to turn off the gas stove after cooking. This type of error has been referred to as an action slip—a form of unintentional behavioral error that occurs when an individual attempts to perform an automatic and/or familiar task. In this case, action slips occurred nine times a day on average and had a serious and long-term impact on the man’s daily quality of life. To reduce the impact of action slips, we created a one-on-one cognitive intervention that used a combination of mnemonic strategies, such as verbalizing his actions as he carried them out, and external aids, including a waist pouch, a voice-controlled artificial intelligence (AI) speaker, and an AI key finder. After 3 years of intervention, the man reported some improvement in his daily activities and a reduction in the number of action slips. Thus, intervention strategies for individuals with a diffuse axonal injury may benefit from targeting action slips. To our knowledge, this is the first detailed description of action slips in an individual with a diffuse axonal injury.
Declines, and Pronounced Regional Disparities, in Meperidine Use in the United States
Authors: Boyle John M. , McCall Kenneth L. , Nichols Stephanie D. , Piper Brian J.
Published: December 2020

Purpose

There have been increasing concerns about adverse effects and drug interactions with meperidine including removal from the World Health Organization’s list of essential medications. The goal of this study was to characterize pharmacoepidemiological patterns in meperidine use in the United States.

Methods

Meperidine distribution data was obtained from the Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS). Medicare Part D Prescriber Public Use Files (PUF) were utilized to capture overall trends in national meperidine prescriptions.

Results

National meperidine distribution decreased from 2001 to 2019 by 94.6%. In 2019 Arkansas, Alabama, Oklahoma, and Mississippi saw significantly greater distribution per person when compared to the average state (9.27, SD = 6.82). Meperidine per ten persons showed an eighteen-fold difference between the highest (Arkansas = 36.8 mg) and lowest (Minnesota = 2.1 mg) states. Five of the six lowest states were in the northeast. Meperidine distribution per state was significantly correlated with the prevalence of adult obesity (r(47) = +0.47,p< 0.001).

Family medicine and internal medicine physicians accounted for 28.9% and 20.5% of Medicare Part D total daily supply (TDS) of meperidine in 2017. However, interventional pain management (5.66) and pain management (3.48) physicians accounted for the longest while family medicine (0.69) and internal medicine (0.40) accounted for the shortest TDS per provider.

Conclusion

Use of meperidine has been declining over the last two-decades. Meperidine distribution varied on a geographical level with south/south-central, and more obese, states showing appreciably greater distribution per person. Primary care doctors continue to account for the majority of meperidine daily supply, but specialists like interventional pain management were the most likely to prescribe meperidine to Medicare patients. Increasing knowledge of meperidine’s undesirable adverse effects (e.g. seizures) and serious drug-drug interactions likely are responsible for these pronounced reductions.
Detection of the Novel SARS-CoV-2 European Lineage B.1.177 in Ontario, Canada
Authors: Guthrie Jennifer L. , Teatero Sarah , Zittermann Sandra , Chen Yao , Sullivan Ashleigh , Rilkoff Heather , Joshi Esha , Sivaraman Karthikeyan , de Borja Richard , Sundaravadanam Yogi , Laszloffy Michael , Heisler Lawrence , Allen Vanessa G. , Simpson Jared T. , Fittipaldi Nahuel
Published: December 2020

Background

Travel-related dissemination of SARS-CoV-2 continues to contribute to the global pandemic. A novel SARS-CoV-2 lineage (B.1.177) reportedly arose in Spain in the summer of 2020, with subsequent spread across Europe linked to travel by infected individuals. Surveillance and monitoring through the use of whole genome sequencing (WGS) offers insights into the global and local movement of pathogens such as SARS-CoV-2 and can detect introductions of novel variants.

Methods

We analyzed the genomes of SARS-CoV-2 sequenced for surveillance purposes from specimens received by Public Health Ontario (Sept 6 – Oct 10, 2020), collected from individuals in eastern Ontario. Taxonomic lineages were identified using pangolin (v2.08) and phylogenetic analysis incorporated publicly available genomes covering the same time period as the study sample. Epidemiological data collected from laboratory requisitions and standard reportable disease case investigation was integrated into the analysis.

Results

Genomic surveillance identified a COVID-19 case with SARS-CoV-2 lineage B.1.177 from an individual in eastern Ontario in late September, 2020. The individual had recently returned from Europe. Genomic analysis with publicly available data indicate the most closely related genomes to this specimen were from Southern Europe. Genomic surveillance did not identify further cases with this lineage.

Conclusions

Genomic surveillance allowed for early detection of a novel SARS-CoV-2 lineage in Ontario which was deemed to be travel related. This type of genomic-based surveillance is a key tool to measure the effectiveness of public health measures such as mandatory self-isolation for returned travellers, aimed at preventing onward transmission of newly introduced lineages of SARS-CoV-2.
Age-Specific Rates of Onset of Cannabis Use in Mexico
Authors: López-Méndez Mauricio , Ospina-Escobar Angélica , Iskandar Rowan , Alarid-Escudero Fernando
Published: December 2020

Background

Over the previous two decades, the prevalence of cannabis use has risen among the population in Mexico.

Aims

To estimate the sex- and age-specific rates of onset of cannabis use over time.

Design

Time-to-event flexible parametric models with spline specifications of the hazard function. Stratified analysis by sex, and control for temporal trends by year of data collection or decennial birth-cohort.

Setting

Mexico.

Participants

Pooled sample of 141,342 respondents aged between 12 and 65 years from five nationally representative cross-sectional surveys, the Mexican National Surveys of Addictions (1998, 2002, 2008, 2012) and the Mexican National Survey on Drugs, Alcohol, and Tobacco Consumption (2016).

Measurements

We estimated age-specific rates of onset of cannabis as the conditional rate of consuming cannabis for the first time at a specific age.

Findings

Age-specific rates of onset of cannabis use per 1,000 individuals increased over time for both females and males. Peak rates per 1,000 ranged from 0.935 (95%CI= [0.754,1.140]) in 1998, to 5.390 (95%CI= [4.910,5.960]) in 2016 for females; and from 7.510 (95%CI= [5.516, 10.355]) in 1998, to 26.100 (95%CI= [23.162,30.169]) in 2016 for males. Across decennial birth-cohorts, peak rates of onset of cannabis use per 1,000 individuals for females ranged from 0.342 (95%CI= [0.127,0.898]) for those born in the 1930s, to 14.600 (95%CI= [13.200,16.100]) for those born in the 1990s; and for males, from 4.900 (95%CI= [0.768, 7.947]) for those born in the 1930s, to 38.700 (95%CI= [32.553,66.341]) for those born in the 1990s.

Conclusion

Rates of onset of cannabis use for males are higher than for females; however, the change across recent cohorts of the rates of onset has increased at a faster rate among females. Our findings can inform and improve the implementation of policies around cannabis use by identifying subpopulations by age, sex, and birth-cohort that are at the highest risk of initiating cannabis consumption.
YeastNet: Deep Learning Enabled Accurate Segmentation of Budding Yeast Cells in Bright-field Microscopy
Authors: Salem Danny , Li Yifeng , Xi Pengcheng , Phenix Hilary , Cuperlovic-Culf Miroslava , Kaern Mads
Published: December 2020

Accurate and efficient segmentation of live-cell images is critical in maximising data extraction and knowledge generation from high-throughput biology experiments. Despite recent development of deep learning tools for biomedical imaging applications, great demand for automated segmentation tools for high-resolution live-cell microscopy images remains in order to accelerate the analysis. YeastNet dramatically improves the performance of non-trainable classic algorithm, and performs considerably better than the current state-of-the-art yeast cell segmentation tools. We have designed and trained a U-Net convolutional network (named YeastNet) to conduct semantic segmentation on bright-field microscopy images and generate segmentation masks for cell labelling and tracking. YeastNet enables accurate automatic segmentation and tracking of yeast cells in biomedical applications. YeastNet is freely provided with model weights as a Python package on GitHub.https://github.com/kaernlab/YeastNet
Assessing deep learning algorithms incis-regulatory motif finding based on genomic sequencing data
Authors: Wang Yan , Zhang Shuangquan , Ma Anjun , Wang Cankun , Wu Zhenyu , Xu Dong , Ma Qin
Published: December 2020

Cis-regulatory motif finding is a crucial step in the detection of gene regulatory mechanisms using genomic data. Deep learning (DL) models have been utilized to denovoly identify motifs, and have been proven to outperform traditional methods. By 2020, twenty DL models have been developed to identify DNA and RNA motifs with diverse framework designs and implementation styles. Hence, it is beneficial to systematically compare their performances, which can facilitate researchers in selecting the appropriate tools for their motif analyses. Here, we carried out an in-depth assessment of the 20 models utilizing 1,043 genomic sequencing datasets, including 690 ENCODE ChIP-Seq, 126 cancer ChIP-Seq, 172 single-cell cleavages under targets and release using a nuclease, and 55 RNA CLIP-Seq. Four metrics were designed and investigated, including the accuracy of motif finding, the performance of DNA/RNA sequence classification, algorithm scalability, and tool usability. The assessment results demonstrated the high complementarity of the existing models, and it was determined that the most suitable model should primarily depend on the data size and type as well as the model outputs. A webserver was developed to allow efficient access of the identified motifs and effective utilization of high-performing DL models.
Liquid foam therapy (LiFT) for homogenous distribution of exogenous pulmonary surfactant in ARDS
Authors: Fishler Rami , Ostrovski Yan , Frenkel Avital , Dorfman Simon , Brod Vera , Haas Tali , Waisman Dan , Sznitman Josué
Published: December 2020

Lung surfactant dysfunction has a critical role in the pathophysiology of acute respiratory distress syndrome (ARDS). Yet, efforts to treat ARDS patients with liquid instillations of exogenous surfactant have so far failed. One of the ongoing challenges in surfactant therapy is obtaining a homogeneous distribution of surfactant within the lungs despite an inherent tendency to non-uniform spreading, owing amongst others to the influence of gravity. Here, we show that liquid foam therapy (LiFT), where surfactant is foamed prior to intratracheal administration, may improve notably surfactant distribution while maintaining safety and efficacy. We first show quantitatively that a foamed surrogate surfactant solution distributes more uniformly inex vivopig lungs compared to endotracheal instillations of the liquid solution, while maintaining pulmonary airway pressures within a safe range. Next, we demonstrate that a foamed commercial surfactant preparation (Infasurf) is effective in an establishedin vivorat lung lavage model of ARDS. Our results suggest that LiFT may be more effective than liquid instillations for treating ARDS and serve as a proof-of-principle towards large animal and clinical trials.
Sex, Competition and Mimicry : an eco-evolutionary model reveals how ecological interactions shape the evolution of phenotypes in sympatry
Authors: Grégoire Boussens-Dumon , Violaine Llaurens
Published: December 2020

1

Phenotypic evolution in sympatric species can be strongly impacted by species interactions, either mutualistic or antagonistic, which may favour local phenotypic divergence or convergence. Interspecific sexual interactions between sympatric species has been shown to favour phenotypic divergence of traits used as sexual cues for example. Those traits may also be involved in local adaptation or in other types of species interactions resulting in complex evolution of traits shared by sympatric species. Here we focus on mimicry and study how reproductive interference may impair phenotypic convergence between species with various levels of defences. We use a deterministic model assuming two sympatric species and where individuals can display two different warning colour patterns. This eco-evolutionary model explores how ecological interactions shape phenotypic evolution within sympatric species. We investigate the effect of (1) the opposing density-dependent selections exerted on colour patterns by predation and reproductive behaviour, and (2) the impact of relative species and phenotype abundances on the fitness costs faced by each individual depending on their species and phenotype. Our model shows that reproductive interference may limit the convergent effect of mimetic interactions and may promote phenotypic divergence between Müllerian mimics. The divergent and convergent evolution of traits also strongly depends on the relative species and phenotype abundances and levels of trophic competition, highlighting how the eco-evolutionary feedbacks between phenotypic evolution and species abundances may result in strikingly different evolutionary routes.
A body map of somatic mutagenesis in morphologically normal human tissues
Authors: Li Ruoyan , Di Lin , Li Jie , Fan Wenyi , Liu Yachen , Guo Wenjia , Liu Weiling , Liu Lu , Li Qiong , Chen Liping , Chen Yamei , Miao Chuanwang , Liu Hongjin , Wang Yuqian , Ma Yuling , Xu Deshu , Lin Dongxin , Huang Yanyi , Wang Jianbin , Bai Fan , Wu Chen
Published: December 2020

Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.
Pollen source richness may be a poor predictor of bumblebee colony growth
Authors: Watrobska Cecylia M. , Rodrigues Ana Ramos , Arce Andres N. , Clarke Jessica , Gill Richard J.
Published: December 2020

Agricultural intensification has drastically altered foraging landscapes for bees, with large-scale crop monocultures associated with floral diversity loss.

Research on bumblebees and honeybees has shown individuals feeding on pollen from a low richness of floral sources can experience negative impacts on health and longevity relative to higher pollen source richness of similar protein concentrations. Florally rich landscapes are thus generally assumed to better support social bees. Yet, little is known about whether the effects of reduced pollen source richness can be mitigated by feeding on pollen with higher crude protein concentration, and importantly how variation in diet affects whole colony growth, rearing decisions and sexual production.

Studying queen-right bumblebee (Bombus terrestris) colonies, we monitored colony development under polyfloral pollen diet or monofloral pollen diet with 1.5-1.8 times higher crude protein concentration.

Over six weeks, we found monofloral colonies performed better for all measures, with no apparent long-term effects on colony mass or worker production, and a higher number of pupae in monofloral colonies at the end of the experiment. Unexpectedly, polyfloral colonies showed higher mortality, and little evidence of any strategy to counteract the effects of reduced protein; with fewer and lower mass workers being reared, and males showing a similar trend.

Our findings i) provide well-needed daily growth dynamics of queenright colonies under varied diets, and ii) support the view that pollen protein content in the foraging landscape rather than floral species richness per se is likely a key driver of colony success.
Integrating thermodynamic and enzymatic constraints into genome-scale metabolic models
Authors: Yang Xue , Mao Zhitao , Zhao Xin , Wang Ruoyu , Zhang Peiji , Cai Jingyi , Ma Hongwu
Published: December 2020

Stoichiometric genome-scale metabolic network models (GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric ratios, other constraints such as enzyme availability and thermodynamic feasibility can also limit the phenotype solution space. Extended GEM models considering either enzymatic or thermodynamic constraints have been shown to improve prediction accuracy. In this paper, we propose a novel method that integrates both enzymatic and thermodynamic constraints in a single Pyomo modeling framework (ETGEMs). We applied this method to construct the EcoETM, theE. colimetabolic model iML1515 with enzymatic and thermodynamic constraints. Using this model, we calculated the optimal pathways for cellular growth and the production of 22 metabolites. When comparing the results with those of iML1515 and models with one of the two constraints, we observed that many thermodynamically unfavorable and/or high enzyme cost pathways were excluded from EcoETM. For example, the synthesis pathway of carbamoyl-phosphate (Cbp) from iML1515 is both thermodynamically unfavorable and enzymatically costly. After introducing the new constraints, the production pathways and yields of several Cbp-derived products (e.g. L-arginine, orotate) calculated using EcoETM were more realistic. The results of this study demonstrate the great application potential of metabolic models with multiple constraints for pathway analysis and phenotype predication.
Nutraceutical profiles of apricots (Prunus armeniacaL.) as a source of fruit quality traits for breeding
Authors: Gómez-Martínez Helena , Bermejo Almudena , Badenes María Luisa , Zuriaga Elena
Published: December 2020

In a social context of increasingly concern about healthy diets, the development of new varieties with enhanced content in nutraceutical compounds is an increasingly important objective of the fruit breeding programs currently developed. In this sense, apricot is a fruit crop very appreciated by consumers due to its organoleptic characteristics, but also plays an important role in human nutrition due to its contain of phytocompounds as sugars, organic acids, vitamins and polyphenols. In this work, new selections from the apricot breeding program carried out at the Instituto Valenciano de Investigaciones Agrarias (IVIA) and traditional varieties have been analysed aimed at identifying sources of genetic variation for fruit quality. For this purpose, sugar content, organic acids and ascorbic acid were studied during two crop years. Results revealed sucrose and glucose as the major sugars, malic and citric acid as the main organic acids, and diverse ascorbic acid content among the cultivars studied. Results obtained pointed some accessions as potential sources to increase fruit quality. In addition, the study showed that apricot peel is an excellent source of nutraceutical compounds. Moreover, this study opens up new possibilities for future work to study the genetic control of these traits in apricot.
Female mice are more prone to develop an addictive-like phenotype for sugar consumption
Authors: Wei Shoupeng , Hertle Sarah , Spanagel Rainer , Bilbao Ainhoa
Published: December 2020

Background

The concept of “sugar addiction” is gaining increasing attention in both the lay media and scientific literature. However, the concept of sugar addiction is controversial and only a few studies have attempted to determine the “addictive” properties of sugar using rigorous scientific criteria.

Objective

Here we set out to systematically test the addictive properties of sugar in male and female mice using established paradigms and models from the drug addiction field.

Methods

Male and female C57BL/6N (8-10 weeks old) were evaluated in 4 experimental procedures to study the addictive properties of sugar: (i) a drinking in the dark (DID) procedure to model sugar binging; (ii) a long-term free choice home cage drinking procedure measuring the sugar deprivation effect (SDE) following an abstinence phase; (iii) a long-term operant sugar self-administration with persistence, motivation and compulsivity measures and (iv) intracranial self-administration (ICSS).

Results

Female mice were more vulnerable to the addictive properties of sugar than male mice, showing higher binge and long-term, excessive drinking, a more pronounced relapse-like drinking following deprivation, and higher persistence and motivation for sugar. No sex differences were seen in a compulsivity test or reward sensitivity measured using ICSS following extended sugar consumption.

Conclusion

This study demonstrates the occurrence of an addictive-like phenotype for sugar in male and female mice, similar to drugs of abuse, and suggests sex-dependent differences in the development of sugar addiction.
Transcriptome analysis for the development of cell-type specific labeling to study olfactory circuits
Authors: Koldaeva Anzhelika , Zhang Cary , Huang Yu-Pei , Reinert Janine , Mizuno Seiya , Sugiyama Fumihiro , Takahashi Satoru , Soliman Taha , Matsunami Hiroaki , Fukunaga Izumi
Published: December 2020

In each sensory system of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at some stage in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, little is known how these two types of projection neurons differ at the mRNA level. Here, we sought to identify genes that are differentially expressed between MCs and TCs, with an ultimate goal to generate a cell-type specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Despite many genes showing differential expressions, we identified only a few that were abundantly and consistently expressed only in MCs. After further validating these putative markers usingin-situhybridization, two genes, namelyPkibandLbdh2, remained as promising candidates. Using CRISPR/Cas9-mediated gene editing, we generated Cre-driver lines and analysed the resulting recombination patterns. This analysis indicated that our new inducible Cre-driver line,Lbhd2-CreERT2, can be used to genetically label MCs in a tamoxifen dose-dependent manner, as assessed by soma locations, projection patterns and sensory-evoked responses. Hence this line is a promising tool for future investigations of cell-type specific contributions to olfactory processing and demonstrates the power of publicly accessible data in accelerating science.
The Bardet-Biedl Syndrome complex component BBS1 regulates proteasome-dependent F-actin clearance from the centrosome to enable its translocation to the T cell immune synapse
Authors: Cassioli Chiara , Onnis Anna , Finetti Francesca , Capitani Nagaja , Compeer Ewoud B , Dustin Micheal L , Baldari Cosima T
Published: December 2020

Components of the intraflagellar transport (IFT) system that regulates the assembly of the primary cilium are exploited by the non-ciliated T cell to orchestrate polarized endosome recycling to sustain signaling during immune synapse formation. Here we have investigated the potential role of BBS1, an essential core component of the Bardet-Biedl syndrome complex that cooperates with the IFT system in ciliary protein trafficking, in the assembly of the T cell synapse. We show that BBS1 allows for centrosome polarization towards the immune synapse by promoting its untethering from the nuclear envelope. This function is achieved through the clearance of centrosomal F-actin and its positive regulator WASH, a process that we demonstrate to be dependent on the proteasome. We show that BBS1 regulates this process by coupling the 19S proteasome regulatory subunit to the microtubule motor dynein for its transport to the centrosome. Our data identify the ciliopathy-related protein BBS1 as a new player in T cell synapse assembly that acts upstream of the IFT system to set the stage for polarized vesicular trafficking and sustained signaling.
Automatic generation of ground truth data for the evaluation of clonal grouping methods in B-cell populations
Authors: Abdollahi Nika , de Septenville Anne , Davi Frédéric , Bernardes Juliana S.
Published: December 2020

Motivation

The adaptive B-cell response is driven by the expansion, somatic hypermutation, and selection of B-cell clones. Their number, size and sequence diversity are essential characteristics of B-cell populations. Identifying clones in B-cell populations is central to several repertoire studies such as statistical analysis, repertoire comparisons, and clonal tracking. Several clonal grouping methods have been developed to group sequences from B-cell immune repertoires. Such methods have been principally evaluated on simulated benchmarks since experimental data containing clonally related sequences can be difficult to obtain. However, experimental data might contains multiple sources of sequence variability hampering their artificial reproduction. Therefore, the generation of high precision ground truth data that preserves real repertoire distributions is necessary to accurately evaluate clonal grouping methods.

Results

We proposed a novel methodology to generate ground truth data sets from real repertoires. Our procedure requires V(D)J annotations to obtain the initial clones, and iteratively apply an optimisation step that moves sequences among clones to increase their cohesion and separation. We first showed that our method was able to identify clonally-related sequences in simulated repertoires with higher mutation rates, accurately. Next, we demonstrated how real benchmarks (generated by our method) constitute a challenge for clonal grouping methods, when comparing the performance of a widely used clonal grouping algorithm on several generated benchmarks. Our method can be used to generate a high number of benchmarks and contribute to construct more accurate clonal grouping tools.

Availability and implementation

The source code and generated data sets are freely available atgithub.com/NikaAb/BCR_GTG
Chromosome-level genome assembly of the common chaffinch (Aves:Fringilla coelebs): a valuable resource for evolutionary biology
Authors: Recuerda María , Vizueta Joel , Cuevas-Caballé Cristian , Blanco Guillermo , Rozas Julio , Milá Borja
Published: December 2020

The common chaffinch,Fringilla coelebs,is one of the most common, widespread and well-studied passerines in Europe, with a broad distribution encompassing Western Europe and parts of Asia, North Africa and the Macaronesian archipelagos. We present a high-quality genome assembly of the common chaffinch generated using Illumina shotgun sequencing in combination with Chicago and Hi-C libraries. The final genome is a 994.87 Mb chromosome-level assembly, with 98% of the sequence data located in chromosome scaffolds and a N50 statistic of 69.73 Mb. Our genome assembly shows high completeness, with a complete BUSCO score of 93.9% using the avian dataset. Around 7.8 % of the genome contains interspersed repetitive elements. The structural annotation yielded 17,703 genes, 86.5% of which have a functional annotation, including 7,827 complete universal single-copy orthologs out of 8,338 genes represented in the BUSCO avian data set. This new annotated genome assembly will be a valuable resource as a reference for comparative and population genomic analyses of passerine, avian and vertebrate evolution.
Inferring system-level brain communication through multi-scale neural activity
Authors: Chang Yin-Jui , Chen Yuan-I , Yeh Hsin-Chih , Carmena Jose M. , Santacruz Samantha R.
Published: December 2020

Fundamental principles underlying computation in multi-scale brain networks illustrate how multiple brain areas and their coordinated activity give rise to complex cognitive functions. Whereas the population brain activity has been studied in the micro-to meso-scale in building the connections between the dynamical patterns and the behaviors, such studies were often done at a single length scale and lacked an explanatory theory that identifies the neuronal origin across multiple scales. Here we introduce the NeuroBondGraph Network, a dynamical system incorporating both biological-inspired components and deep learning techniques to capture cross-scale dynamics that can infer and map the neural data from multiple scales. We demonstrated our model is not only 3.5 times more accurate than the popular sphere head model but also able to predict synchronous neural activity and extract correlated low-dimensional latent dynamics. We also showed that we can extend our methods to robustly predict held-out data across several weeks. The extracted effective connectivity agreed with the neuroanatomical hierarchy of motor control. Accordingly, the NeuroBondGraph Network opens the door to revealing comprehensive understanding of the brain computation, where network mechanisms of multi-scale communications are critical.
Comparative Analysis of Embryo Proper and Suspensor Transcriptomes in Plant Embryos With Different Morphologies
Authors: Chen Min , Lin Jer-Young , Wu Xiaomeng , Apuya Nestor R. , Henry Kelli F. , Le Brandon H. , Bui Anhthu Q. , Pelletier Julie M. , Cokus Shawn , Pellegrini Matteo , Harada John J. , Goldberg Robert B.
Published: December 2020

An important question is what genes govern the differentiation of plant embryos into suspensor and embryo-proper regions following fertilization and division of the zygote. We compared embryo proper and suspensor transcriptomes of four plants that vary in embryo morphology within the suspensor region. We determined that genes encoding enzymes in several metabolic pathways leading to the formation of hormones, such as gibberellic acid, and other metabolites are up-regulated in giant Scarlet Runner Bean and Common Bean suspensors. Genes involved in transport and Golgi body organization are up-regulated within the suspensors of these plants as well – strengthening the view that giant specialized suspensors serve as a hormone factory and a conduit for transferring substances to the developing embryo proper. By contrast, genes controlling transcriptional regulation, development, and cell division are up-regulated primarily within the embryo proper. Transcriptomes from less specialized soybean andArabidopsissuspensors demonstrated that fewer genes encoding metabolic enzymes and hormones are up-regulated. Genes active in the embryo proper, however, are functionally similar to those active in Scarlet Runner Bean and Common Bean embryo proper regions. We uncovered a set of suspensor- and embryo-proper-specific transcription factors (TFs) that are shared by all embryos irrespective of morphology, suggesting that they are involved in early differentiation processes common to all plants. ChIP-Seq experiments with Scarlet Runner Bean and soybean WOX9, an up-regulated suspensor TF, gained entry into a regulatory network important for suspensor development irrespective of morphology.

Significance

How plant embryos are differentiated into embryo proper and suspensor regions following fertilization is a major unanswered question. The suspensor is unique because it can vary in morphology in different plant species. We hypothesized that regulatory genes controlling the specification of embryo proper and suspensor regions should be shared by all plants irrespective of embryo morphology. We compared embryo proper and suspensor transcriptomes of plants with distinct suspensor morphologies. Scarlet Runner Bean and Common Bean have highly specialized giant suspensor regions, whereas soybean andArabidopsissuspensors are smaller and less specialized. We uncovered a small set of embryo-proper- and suspensor-specific transcription factors shared by all embryos irrespective of morphology, suggesting that they play an important role in early embryo differentiation.
Suppressing the morning cortisol rise after memory reactivation at 4 a.m. enhances episodic memory reconsolidation in humans
Authors: Antypa Despina , Perrault Aurore A. , Vuilleumier Patrik , Schwartz Sophie , Rimmele Ulrike
Published: December 2020

Evidence from animal and human research shows that established memories can undergo changes after reactivation through a process called reconsolidation. Alterations of the level of the stress hormone cortisol may be one way of manipulating reconsolidation. Here, in a double-blind, within-subject design, we reactivated a 3-day-old memory at 3:55 a.m., immediately followed by oral administration of metyrapone vs. placebo, to examine whether metyrapone-induced suppression of the morning cortisol rise may influence reconsolidation processes during and after early morning sleep. Crucially, reactivation followed by cortisol suppression vs. placebo resulted in enhanced memory for the reactivated episode (tested four days after reactivation). This enhancement after cortisol suppression was specific for the reactivated episode vs. a non-reactivated episode. These findings suggest that when reactivation of memories is immediately followed by suppression of cortisol levels during early morning sleep, reconsolidation processes change in a way that leads to the strengthening of episodic memory traces.
Enhancing daily light exposure increases the antibody response to influenza vaccination in patients with dementia
Authors: Münch Mirjam , Goldbach Rolf , Zumstein Naomi , Vonmoos Petra , Scartezzini Jean-Louis , Wirz-Justice Anna , Cajochen Christian
Published: December 2020

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we tested whether a greater long-term daily light exposure supports the immune response to the annual influenza vaccination. Eighty older institutionalised patients suffering from dementia (54 women and 26 men) continuously wore an activity tracker for 8 weeks to assess individual light exposure and rest-activity cycles. The patients’ immune response was analysed from two blood samples taken before and 4 - 5 weeks after the annual influenza vaccination. Individual antibody concentrations to three influenza virus strains (H3N2, H1N1, IB) were quantified via hemagglutination inhibition assays. By quantifying individual light exposure profiles (including daylight), we classified the patients into a low and a high light exposure group based on a median illuminance of 392.6 lux. The two light exposure groups did not differ in cognitive impairment severity, age or gender distribution. However, patients in the high light exposure group showed a significantly greater circadian rest-activity amplitude (i.e., more daytime activity and less nighttime activity) along with a significantly greater antibody titer increase to the H3N2 vaccine than patients in the low light exposure group, despite similar pre-vaccination concentrations. Sufficient seroprotective responses to all three influenza virus strains were attained for ≥ 75% of participants. These data provide first evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Increasing daily light exposure may have beneficial effects on the human immune system, either directly or via circadian rhythm stabilisation.
Bacillus subtilisYngB contributes to wall teichoic acid glucosylation and glycolipid formation during anaerobic growth
Authors: Wu Chih-Hung , Rismondo Jeanine , Morgan Rhodri M. L. , Shen Yang , Loessner Martin J. , Larrouy-Maumus Gerald , Freemont Paul S. , Gründling Angelika
Published: December 2020

UTP-glucose-1-phosphate uridylyltransferases (UGPases) are enzymes that produce UDP-glucose from UTP and glucose-1-phosphate. InBacillus subtilis168, UDP-glucose is required for the decoration of wall teichoic acid (WTA) with glucose residues and the formation of glucolipids. TheB. subtilisUGPase GtaB is essential for UDP-glucose production under standard aerobic growth conditions, andgtaBmutants display severe growth and morphological defects. However, bioinformatics predictions indicate that two other UGPases, are present inB. subtilis. Here, we investigated the function of one of them named YngB. The crystal structure of YngB revealed that the protein has the typical fold and all necessary active site features of a functional UGPase. Furthermore, UGPase activity could be demonstratedin vitrousing UTP and glucose-1-phosphate as substrates. Expression of YngB from a synthetic promoter in aB. subtilis gtaBmutant resulted in the reintroduction of glucose residues on WTA and production of glycolipids, demonstrating that the enzyme can function as UGPasein vivo. When wild-type and mutantB. subtilisstrains were grown under anaerobic conditions, YngB-dependent glycolipid production and glucose decorations on WTA could be detected, revealing that YngB is expressed from its native promoter under anaerobic condition. Based on these findings, along with the structure of the operon containingyngBand the transcription factor thought to be required for its expression, we propose that besides WTA, potentially other cell wall components might be decorated with glucose residues during oxygen limited growth condition.