bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Clinical Course from Subcortical Shape in Provisional Tic Disorder
Authors: Che Tiffanie , Kim Soyoung , Greene Deanna J. , Heywood Ashley , Ding Jimin , Hershey Tamara , Schlaggar Bradley L. , Black Kevin J. , Wang Lei
Published: November 2021

The NewTics study examined children at the onset of tic disorder (with tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the shape of subcortical nuclei and tic symptom outcomes. 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder or Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic metric mapping, and linear regression models were constructed to correlate baseline structural shapes with follow-up TTS while accounting for covariates, with relationships mapped onto structure surfaces. We found that the NT group had a larger right hippocampus compared to healthy controls. Surface maps illustrate distinct patterns of inward deformation (localized lower volume) in the putamen and outward deformation (localized volume gain) in the thalamus for the NT group compared to healthy controls. We also found distinct patterns of outward deformation in almost all studied structures when comparing the TS group to healthy controls. In the significant vertices of this comparison, the caudate further exhibited an overall trend of greater outward deformation (compared to the template) in the TS group compared to both the NT group and controls. When comparing the NT and TS groups, the NT group showed consistent outward deformation in the caudate, accumbens, putamen, and thalamus. Since the NT group has had tics only for a few months, we can rule out the possibility that these subcortical volume differences are caused by living with tics for years; they are more likely related to the cause of tics. Subsequent analyses including clinical symptoms revealed that a larger pallidum and thalamus at baseline predicted less improvement of tic symptoms in the future. These observations constitute some of the first prognostic biomarkers for tic disorders and suggest that these subregional volume differences may be associated with outcome of tic disorders.
Multiplexed micronutrient, inflammation, and malarial antigenemia assessment using a plasma fractionation device
Authors: Brindle Eleanor , Lillis Lorraine , Barney Rebecca , Bansil Pooja , Arredondo Francisco , Craft Neal E. , Murphy Eileen , Boyle David S.
Published: November 2021

Collecting, processing, and storing blood samples for future analysis of biomarkers can be challenging when performed in resource limited environments. The preparation of dried blood spots (DBS) from heel or finger stick collection of whole blood is a widely used and established method. DBS pose less risk of infection from blood borne pathogens, do not require immediate specimen processing and tolerate a wider range of storage temperatures, and are easier to ship. As such, DBS are commonly used in large-scale surveys to assess infectious disease status and/or micronutrient status in vulnerable populations. Recently, we reported that DBS can be used with a multiplexed immunoassay, the Q-plex™ Human Micronutrient 7-plex Array (MN 7-plex). This tool can simultaneously quantify seven protein biomarkers related to micronutrient deficiencies (iodine, iron and vitamin A), inflammation and malarial antigenemia using plasma or serum. Serum ferritin, a key iron biomarker, cannot be measured from DBS due to red blood cell (RBC) ferritin confounding the results. In this study, we demonstrate the performance of a simple and rapid blood fractionation tool that passively separates serum from cellular components via diffusion through a membrane into a plasma collection disc (PCD) to produce plasma spots. We evaluated the concordance of MN 7-plex analyte concentrations from matched panels of eighty-eight samples of PCD, DBS, and wet plasma prepared from anticoagulated venous whole blood. The results show high correlation between eluates from PCD and DBS and wet plasma for each analyte. Serum ferritin measures from the PCD eluates were highly correlated to wet plasma samples. This suggests that surveillance for iron deficiency may be improved over the current methods restricted to only measuring sTfR in DBS as when used in combination with the MN 7-plex, all seven biomarkers can be simultaneously measured using PCDs.
Is modular control related to functional outcomes in individuals with knee osteoarthritis and following total knee arthroplasty?
Authors: Koehn Rebekah R. , Roelker Sarah A. , Pan Xueliang , Schmitt Laura C. , Chaudhari Ajit M.W. , Siston Robert A.
Published: November 2021

Background

Individuals who undergo total knee arthroplasty (TKA) for treatment of knee osteoarthritis often experience suboptimal outcomes. Investigation of neuromuscular control strategies in these individuals may reveal factors that contribute to these functional deficits. The purpose of this pilot study was to determine the relationship between patient function and modular control during gait before and after TKA.

Methods

Electromyography data from 36 participants (38 knees) were collected from 8 lower extremity muscles on the TKA-involved limb during ≥5 over-ground walking trials before (n=30), 6-months after (n=26), and 24-months after (n=13) surgery. Muscle modules were estimated using non-negative matrix factorization. The number of modules was determined from 500 resampled trials.

Results

A higher number of modules was related to better performance-based and patient-reported function before and 6-months after surgery. Participants with organization similar to healthy, age-matched controls trended toward better function 24-months after surgery, though these results were not statistically significant. We also observed plasticity in the participants’ modular control strategies, with 100% of participants who were present before and 24-months after surgery (10/10) demonstrating changes in the number of modules and/or organization of at least 1 module.

Conclusions

This pilot work suggests that functional improvements following TKA may initially present as increases in the number of modules recruited during gait. Subsequent improvements in function may present as improved module organization.

Noteworthy

This work is the first to characterize motor modules in TKA both before and after surgery and to demonstrate changes in the number and organization of modules over the time course of recovery, which may be related to changes in patient function. The plasticity of modular control following TKA is a key finding which has not been previously documented and may be useful in predicting or improving surgical outcomes through novel rehabilitation protocols.
Longitudinal Changes of Cardiac and Aortic Imaging Phenotypes Following COVID-19 in the UK Biobank Cohort
Authors: Bai Wenjia , Raman Betty , Petersen Steffen E. , Neubauer Stefan , Raisi-Estabragh Zahra , Aung Nay , Harvey Nicholas C , Allen Naomi , Collins Rory , Matthews Paul M.
Published: November 2021

Case studies conducted after recovery from acute infection with SARS-CoV-2 have frequently identified abnormalities on CMR imaging, suggesting the possibility that SARS-CoV-2 infection commonly leads to cardiac pathology. However, these observations have not been able to distinguish between associations that reflect pre-existing cardiac abnormalities (that might confer a greater likelihood of more severe infection) from those that arise as consequences of infection. To address this question, UK Biobank volunteers (n=1285; 54.5% women; mean age at baseline, 59.8 years old; 96.3% white) who attended an imaging assessment including cardiac magnetic resonance (CMR) before the start of the COVID-19 pandemic were invited to attend a second imaging assessment in 2021. Cases with evidence of previous SARS-CoV-2 infection were identified through linkage to PCR-testing or other medical records, or a positive antibody lateral flow test; n=640 in data available on 22 Sep 2021) and were matched to controls with no evidence of previous infection (n=645). The majority of these infections were milder and did not involve hospitalisation. Measures of cardiac and aortic structure and function were derived from the CMR images obtained on the cases before and after SARS-CoV-2 infection from images for the controls obtained over the same time interval using a previously validated, automated algorithm. Cases and controls had similar cardiac and aortic imaging phenotypes at their first imaging assessment. Changes between CMR imaging measures in cases before and after infection were not significantly different from those in the matched control group. Additional adjustment for comorbidities made no material difference to the results. While these results are preliminary and limited to imaging metrics derived from automated analyses, they do not suggest clinically significant persistent cardiac pathology in the UK Biobank population after generally milder (non-hospitalised) SARS-CoV-2 infection.
Estimation of the basic reproduction number of COVID-19 from the incubation period distribution
Authors: Basnarkov Lasko , Tomovski Igor , Avram Florin
Published: November 2021

Background

The estimates of future course of spreading of the SARS-CoV-2 virus are frequently based on Markovian models in which the transitions between the compartments are exponentially distributed. Specifically, the basic reproduction number R0 is also determined from formulae where it is related to the parameters of such models. The observations show that the start of infectivity of an individual appears nearly at the same time as the onset of symptoms, while the distribution of the incubation period is not an exponential.

Methods

We propose a method for estimation of R0 for COVID-19 based on the empirical incubation period distribution and assumed very short infectivity period that lasts only few days around the onset of symptoms. It is tested on daily new cases in six major countries in Europe, in the first wave of epidemic in spring, 2020.

Results

The calculations show that even if the infectivity starts two days before the onset of symptoms and stops immediately when they appear, the value of R0 is larger than that from the classical, Markovian approach. For more realistic cases, when only individuals with mild symptoms spread the virus for few days after onset of symptoms, the respective values are even larger.

Conclusions

The calculations of R0 and other characteristics of spreading of COVID-19 based on the classical, Markovian approaches should be taken very cautiously. Instead, non-Markovian models with general distribution functions of transition between compartments should be considered as more appropriate.

Key messages

Although formulae for estimate of the basic reproduction number R0, by using general-form functions of infectivity are known since the earliest works in epidemiology, majority of studies are based on exponential distribution function.

We introduce a new methodology of calculating R0 with an infectivity function obtained by combining empirical incubation period distribution with infectivity window function that is localized around the onset of symptoms.

Estimates of R0 for the first wave of COVID - 19 in the spring 2020, by the proposed methodology are larger than those from the classical SIR model.

When possible, the estimates of R0 should be based on empirical distributions of the infectivity functions, while the values obtained with the conventional epidemic spreading models should be taken with caution.
Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer disease brains
Authors: Novotny Brenna C , Fernandez Maria Victoria , Wang Ciyang , Budde John P , Bergmann Kristy , Eteleeb Abdallah , Bradley Joseph , Webster Carol , Ebl Curtis , Norton Joanne , Gentsch Jen , Dube Umber , Wang Fengxian , Morris John C , Bateman Randall J , Perrin Richard J , McDade Eric , Xiong Chengjie , Chhatwal Jasmeer ,   Dominantly Inherited Alzheimer Network Study Group,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium, Goate Alison , Farlow Martin , Schofield Peter , Chui Helena , Karch Celeste M , Benitez Bruno A , Cruchaga Carlos , Harari Oscar
Published: November 2021

The identification of multiple genetic risk factors for Alzheimer Disease (AD) provides evidence to support that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain, including information on treatment targets. In this study, we interrogate the metabolomic and lipidomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE ε4 and TREM2 risk variant carriers, and non-carrier sporadic AD (sAD). We generated metabolomic and lipidomic data from parietal cortical tissue from 366 participants with AD pathology and 26 cognitively unimpaired controls using the Metabolon global metabolomics platform. We identified 133 metabolites associated with disease status (FDR q-value<0.05). In sAD brains these include tryptophan betaine (b=-0.57) and N-acetylputrescine (b=-0.14). Metabolites associated with sAD and ADAD include ergothioneine (b=-0.21 and -0.26 respectively) and serotonin (b=-0.34 and -0.58, respectively). TREM2 and ADAD showed association with α-tocopherol (b=-0.12 and -0.12) and CDP-ethanolamine (b=-0.13 and -0.10). β-citrylglutamate levels are associated with sAD, ADAD, and TREM2 compared to controls (b=-0.15; -0.22; and -0.29, respectively). Additionally, we identified a signature of 16 metabolites that is significantly altered between genetic groups (sAD vs. control p = 1.05×10-7, ADAD vs. sAD p = 3.21×10-5) and is associated with Braak tau stage and disease duration. These data are available to the scientific community through a public web browser (http://ngi.pub/Metabolomics). Our findings were replicated in an independent cohort of 327 individuals.
Sulfite preservatives effects on the mouth microbiome: changes in viability, diversity and composition of microbiota
Authors: Irwin Sally V , Deardorff Luz Maria , Deng Youping , Fisher Peter , Gould Michelle , June Junnie , Kent Rachael S. , Qin Yujia , Yadao Fracesca
Published: November 2021

Processed foods make up about 70 percent of the American diet. Sulfites and other food preservatives are added to these foods largely to limit bacterial contamination. The mouth microbiota and its associated enzymes are the first to encounter food and therefore likely to be the most affected.

Eight saliva samples from ten individuals were exposed to two sulfite preservatives, sodium sulfite and sodium bisulfite. One sample set was evaluated for bacteria composition utilizing 16s rRNA sequencing, and the number of viable cells in all sample sets was determined utilizing ATP assays at 10 and 40-minute exposure times. All untreated samples were analyzed for baseline lysozyme activity, and possible correlations between the number of viable cells and lysozyme activity.

Sequencing results indicated significant increases in alpha diversity with sodium bisulfite exposure and changes in relative abundance of 3 amplicon sequence variants (ASV). Sodium sulfite treated samples showed a significant decrease in the Firmicutes/Bacteroidetes ratio, a marginally significant change in alpha diversity, and a significant change in the relative abundance for Proteobacteria, Firmicutes, Bacteroidetes, and for 6 ASVs. Beta diversity didn’t show any separation between groups, however, all but one sample set was observed to be moving in the same direction under sodium sulfite treatment in a principal component analysis.

ATP assays indicated a significant and consistent average decrease in activity ranging from 24 - 46% at both exposure times with both sulfites.

Average initial rates of lysozyme activity between all individuals ranged from +/- 76% compared to individual variations of +/- 10 - 34%. No consistent, significant correlation was found between ATP and lysozyme activity in any sample sets.

Conclusions

Sulfite preservatives, at concentrations regarded as safe by the FDA, alter the relative abundance and richness of the microbiota found in saliva, and decrease the number of viable cells, within 10 minutes of exposure.
The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
Authors: Abdelnabi Rana , Foo Caroline S. , Jochmans Dirk , Vangeel Laura , De Jonghe Steven , Augustijns Patrick , Mols Raf , Weynand Birgit , Wattanakul Thanaporn , Hoglund Richard M. , Tarning Joel , Mowbray Charles E. , Sjö Peter , Escudié Fanny , Scandale Ivan , Chatelain Eric , Neyts Johan
Published: November 2021

There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.
Absence of enterotypes in the human gut microbiomes reanalyzed with non-linear dimensionality reduction methods
Authors: Bulygin Ivan , Shatov Vladislav , Rykachevsky Anton , Rayko Arseny , Bernstein Alexander , Burnaev Evgeny , Gelfand Mikhail S.
Published: November 2021

Enterotypes of the human gut microbiome have been proposed to be a powerful prognostic tool to evaluate the correlation between lifestyle, nutrition, and disease. However, the number of enterotypes suggested in the literature ranged from two to four. The growth of available metagenome data and the use of exact, non-linear methods of data analysis challenges the very concept of clusters in the multidimensional space of bacterial microbiomes. Using several published human gut microbiome datasets, we demonstrate the presence of a lower-dimensional structure in the microbiome space, with high-dimensional data concentrated near a low-dimensional non-linear submanifold, but the absence of distinct and stable clusters that could represent enterotypes. This observation is robust with regard to diverse combinations of dimensionality reduction techniques and clustering algorithms.
How low can you go: sex identification from low-quantity sequencing data despite lacking assembled sex chromosomes
Authors: Cabrera Andrea A. , Rey-Iglesia Alba , Louis Marie , Skovrind Mikkel , Westbury Michael V , Lorenzen Eline D
Published: November 2021

Accurate sex identification is crucial for elucidating the biology of a species. In the absence of directly observable sexual characteristics, sex identification of wild fauna can be challenging, if not impossible. Molecular sexing offers a powerful alternative to morphological sexing approaches. Here, we present SeXY, a novel sex-identification pipeline, for very low-coverage shotgun sequencing data from a single individual. SeXY was designed to utilise low-effort screening data for sex identification and does not require a conspecific sex-chromosome assembly as reference. We assess the accuracy of our pipeline to data quantity by downsampling sequencing data from 100,000 to 1,000 mapped reads, and to reference genome selection by mapping to a variety of reference genomes of various qualities and phylogenetic distance. We show that our method is 100% accurate when mapping to a high-quality (highly contiguous N50 > 30 Mb) conspecific genome, even down to 1,000 mapped reads. For lower-quality reference assemblies (N50 < 30 Mb), our method is 100% accurate with 50,000 mapped reads, regardless of reference assembly quality or phylogenetic distance. The SeXY pipeline provides several advantages over previously implemented methods; SeXY (i) requires sequencing data from only a single individual, (ii) does not require assembled conspecific sex-chromosomes, or even a conspecific reference assembly, (iii) takes into account variation in coverage across the genome, and (iv) is accurate with only 1,000 mapped reads in many cases.
Age-Volume Associations in Cerebellar Regions by Sex and Reproductive Stage
Authors: Hicks Tracey H. , Ballard Hannah K. , Sang Huiyan , Bernard Jessica A.
Published: November 2021

Introduction

The cerebellum has established associations with motor function and a well- recognized role in cognition. In advanced age, cognitive and motor impairments contribute to reduced quality of life and are more common. Regional cerebellar volume is associated with performance across these domains and sex hormones may influence this volume. Examining sex differences in regional cerebellar volume in conjunction with age, and in the context of reproductive stage stands to improve our understanding of cerebellar aging and pathology.

Methods

Data from 530 healthy adults (ages 18-88; 49% female) from the Cambridge Centre for Ageing and Neuroscience database were used here. CERES was utilized to assess lobular volume in T1-weighted images. We examined sex differences in adjusted regional cerebellar volume while controlling for age. A subgroup (n = 354, 50% female) was used to assess group differences in female reproductive stages as compared to age-matched males.

Results

Sex differences in adjusted volume were seen across most anterior and posterior cerebellar lobules. The majority of cerebellar regions had significant linear relationships with age in males and females. However, there were no interactions between sex and reproductive stage groups (i.e., female reproductive stage did not display a relationship with regional cerebellar volume).

Discussion

We found sex differences in volume across much of the cerebellum, linear associations with age, and did not find an effect of female reproductive stage on regional cerebellar volume. Longitudinal investigation into hormonal influences on cerebellar structure and function is warranted as hormonal changes with menopause may impact structure over time.
Increased Occurrence of Treponema spp. and Double-species Infections in Patients with Alzheimer’s Disease
Authors: Nemergut Michal , Batkova Tereza , Vigasova Dana , Bartos Milan , Hlozankova Martina , Schenkmayerova Andrea , Liskova Barbora , Sheardova Katerina , Vyhnalek Martin , Hort Jakub , Laczo Jan , Kovacova Ingrid , Sitina Michal , Matej Radoslav , Jancalek Radim , Marek Martin , Damborsky Jiri
Published: November 2021

Objective

Although the link between microbial infections and Alzheimer’s disease (AD) has been demonstrated in multiple studies, the involvement of pathogens in the development of AD remains unclear. Therefore, this theory beckons further systematic investigation. In this study, we have examined the association between the 10 most widely discussed viral and bacterial pathogens found in serum and cerebrospinal fluid (CSF) from patients with AD.

Methods

We have used an in-house developed multiplex PCR kit for simultaneous detection of five bacterial and five viral pathogens in serum and CSF from 50 AD patients and 53 healthy controls. Data analysis was performed with multiple statistical methods: Fisher’s exact test, chisquare goodness of fit test, and one-sample proportion test.

Results

We observed an increased frequency of AD patients tested positive for Treponema spp. (AD: 62.2%; CTRL: 30.3%; p-value = 0.007). Furthermore, we confirmed a significantly higher prevalence of cases with two and more simultaneous infections in AD patients compared to controls (AD: 24%; CTRL 7.5%; p-value = 0.029). The studied pathogens were widespread equally in serum and CSF. Borrelia burgdorferi, human herpesvirus 7, and human cytomegalovirus were not detected in any of the studied samples.

Discussion

An increased prevalence of Treponema spp. and double-species infections in AD patients compared to the healthy controls provides further evidence of the association between microbial infections and AD. Paralleled analysis of multiple sample specimens provides complementary information and is advisable for future studies.
Multi-omics analysis for potential inflammation-related genes involved in tumor immune evasion via extended application of epigenetic data
Authors: Huang Chenshen , Wang Ning , Zhang Na , Ni Zhizhan , Liu Xiaohong , Xiong Hao , Xie Huahao , Lin Boxu , Ge Bujun , Huang Qi , Du Bing
Published: November 2021

Background

Accumulating evidence suggests that inflammation-related genes may play key roles in tumor immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating antitumor immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression.

Methods

The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments.

Results

We identified chr9:5449463-5449962 and chr9:5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results.

Conclusion

Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumor immune evasion in cancers, suggesting the potential value for tumor treatment.
Plant-derived insulator-like sequences for control of transgene expression
Authors: Park Jubilee Y. , Kovar Lynsey , LaFayette Peter R. , Wallace Jason G. , Parrott Wayne A.
Published: November 2021

Stable and consistent transgene expression is necessary to advance plant biotechnology. Stable expression can be achieved by incorporating enhancer-blocking insulators, which are cis-regulatory elements that reduce enhancer interference in gene expression, into transgene constructs. Sufficient insulators for plant use are not available, and their discovery has remained elusive. In this work, we computationally mined the compact genome of Utricularia gibba for insulator sequences and identified short (<1 kb) sequences with potential insulator activity. Based on in vivo tests, three of these effectively mitigate the ectopic transgene expression caused by the Cauliflower Mosaic Virus 35S promoter and do so better than previously reported plant insulators. However, all sequences with apparent insulator activity also decrease the effectiveness of the CaMV 35S promoter, and thus may be more accurately classified as silencers. However, since the insulator effect is proportionately much higher than the silencing effect, these sequences are still useful for plant transformation.
Motor response vigour and fixations reflect subjective preferences during intertemporal choice
Authors: Smith Elke , Peters Jan
Published: November 2021

Value-based decision-making is of central interest in cognitive neuroscience and psychology, as well as in the context of neuropsychiatric disorders characterised by decision-making impairments. Studies examining (neuro-)computational mechanisms underlying choice behaviour typically focus on participants’ decisions. However, there is increasing evidence that option valuation might also be reflected in motor response vigour and eye movements, implicit measures of subjective utility.

To examine motor response vigour and visual fixation correlates of option valuation in intertemporal choice, we set up a task where the participants selected an option by pressing a grip force transducer, simultaneously tracking fixation shifts between options. As outlined in our preregistration (https://osf.io/k6jct), we used hierarchical Bayesian parameter estimation to model the choices assuming hyperbolic discounting, compared variants of the softmax and drift diffusion model, and assessed the relationship between response vigour and the estimated model parameters.

The behavioural data were best explained by a drift diffusion model specifying a non-linear scaling of the drift rate by the subjective value differences. Replicating previous findings (Green et al., 1997; Wagner et al., 2020), we found a magnitude effect for temporal discounting, such that higher rewards were discounted less. This magnitude effect was further reflected in response vigour, such that stronger forces were exerted in the high vs. the low magnitude condition. Bayesian hierarchical linear regression further revealed higher grip forces, faster response times and a lower number of fixation shifts for trials with higher subjective value differences.

Our data suggest that subjective utility or implicit valuation is reflected in response vigour during intertemporal choice. Taking into account response vigour might thus provide deeper insight into decision-making, reward valuation and maladaptive changes in these processes, e.g. in the context of neuropsychiatric disorders.
Glioma synapses recruit mechanisms of adaptive plasticity
Authors: Taylor Kathryn R. , Barron Tara , Zhang Helena , Hui Alexa , Hartmann Griffin , Ni Lijun , Venkatesh Humsa S. , Du Peter , Mancusi Rebecca , Yalçin Belgin , Chau Isabelle , Ponnuswami Anitha , Aziz-Bose Razina , Monje Michelle
Published: November 2021

The nervous system plays an increasingly appreciated role in the regulation of cancer. In malignant gliomas, neuronal activity drives tumor progression not only through paracrine signaling factors such as neuroligin-3 and brain-derived neurotrophic factor (BDNF)1–3, but also through electrophysiologically functional neuron-to-glioma synapses4–6. Malignant synapses are mediated by calcium-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors in both pediatric and adult high-grade gliomas4, 5, and consequent depolarization of the glioma cell membrane drives tumor proliferation4. The nervous system exhibits plasticity of both synaptic connectivity and synaptic strength, contributing to neural circuit form and functions. In health, one factor that promotes plasticity of synaptic connectivity7, 8 and strength9–13 is activity-regulated secretion of the neurotrophin BDNF. Here, we show that malignant synapses exhibit similar plasticity regulated by BDNF-TrkB (tropomyosin receptor kinase B) signaling. Signaling through the receptor TrkB14, BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. This potentiation of malignant synaptic strength shares mechanistic features with the long-term potentiation (LTP)15–23 that is thought to contribute to memory and learning in the healthy brain22 24–27 28, 29. BDNF-TrkB signaling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of TrkB in human glioma cells exerts growth inhibitory effects in vivo and in neuron:glioma co-cultures that cannot be explained by classical growth factor signaling alone. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of pediatric glioblastoma and diffuse intrinsic pontine glioma (DIPG). Taken together, these findings indicate that BDNF-TrkB signaling promotes malignant synaptic plasticity and augments tumor progression.
Complete genome sequence and Benzophenone-3 mineralisation potential of Rhodococcus sp. USK10, a bacterium isolated from riverbank sediment
Authors: Martin Joseph Donald , Krüger Urse Scheel , Zervas Athanasios , Schostag Morten Dencker , Nielsen Tue Kjærgaard , Aamand Jens , Hansen Lars Hestbjerg , Ellegaard-Jensen Lea
Published: November 2021

Benzophenone-3 (BP3) is an organic UV filter whose presence in the aquatic environment has been linked to detrimental developmental impacts in aquatic organisms such as coral and fish. The genus Rhodococcus has been extensively studied and is known for possessing large genomes housing genes for biodegradation of a wide range of compounds, including aromatic carbons. Here, we present the genome sequence of Rhodococcus sp. USK10, which was isolated from Chinese riverbank sediment and is capable of utilising BP3 as the sole carbon source, resulting in full BP3 mineralisation. The genome consisted of 9,870,030 bp in 3 replicons, a G+C content of 67.2%, and 9,722 coding DNA sequences (CDSs). Annotation of the genome revealed that 179 of these CDSs are involved in metabolism of aromatic carbons. The complete genome of Rhodococcus sp. USK10 is the first complete, annotated genome sequence of a Benzophenone-3 degrading bacterium. Through radiolabelling, it is also the first bacterium proven to mineralise Benzophenone-3. Due to the widespread environmental prevalence of Benzophenone-3, coupled to its adverse impact on aquatic organisms, this characterisation provides an integral first step in better understanding the environmentally relevant degradation pathway of the commonly used UV filter. Given USK10’s ability to completely mineralise Benzophenone-3, it could prove to be a suitable candidate for bioremediation application.
Gene essentiality in cancer cell lines is modified by the sex chromosomes
Authors: Shohat Shahar , Vol Ethel , Shifman Sagiv
Published: November 2021

Human sex differences are thought to arise from gonadal hormones and genes on the sex chromosomes. Here we studied how sex and the sex chromosomes can modulate the outcome of mutations across the genome. We used the results of genome-wide CRISPR-based screens on 306 female and 396 male cancer cell lines to detect differences in gene essentiality between the sexes. By exploiting the tendency of cancer cells to lose or gain sex chromosomes, we were able to dissect the contribution of the Y and X chromosomes to variable gene essentiality. Using this approach, we identified 178 differentially essential genes that depend on the biological sex or the sex chromosomes. Integration with sex bias in gene expression and the rate of somatic mutations in human tumors highlighted genes that escape from X-inactivation, cancer-testis antigens, and Y-linked paralogs as central to the functional genetic differences between males and females.
Wild birds as reservoirs of multidrug-resistant enterobacteria in Mulungu, Brazil
Authors: Beleza Antonio Jackson Forte , Maciel William Cardoso , Carreira Arianne Silva , Marques Adson Ribeiro , Nogueira Carlos Henrique Guedes , Filho Neilton Monteiro Pascoal , Lima Bruno Pessoa , da Silva Isaac Neto Goes , Vasconcelos Ruben Horn , Ribeiro Leandro Rodrigues , de Castro Teixeira Régis Siqueira
Published: November 2021

Caatinga is a biome unique to Brazil that is degraded by anthropogenic actions, which lead to the loss of biodiversity putting many species at risk of extinction. The Ceará State is located in the Caatinga and has a rich avifauna comprised of 433 species including 13 species that are threatened with extinction, which are found in the Baturité Massif. The aim of this study was to investigate the frequency and diversity of enterobacteria in wild birds and to determine their susceptibility to antimicrobials. Cloacal swab samples were collected from 50 individuals of 28 different species, including the Ceara Gnatheter (Conopophaga cearae) and Red-necked Tanager (Tangara cyanocephala cearensis), which are classified as vulnerable (VU) by the Brazilian Ministry of the Environment. A total of 55 isolates belonging to 14 different species of Enterobacteriaceae were identified. Among these, Pantoea agglomerans and Escherichia coli were the most prevalent species with isolation rates of 36% and 26%, respectively. The highest rate of antimicrobial resistance found was to ampicillin (41.8%), followed by nalidixic Acid (36.3%) and amoxicillin associated with clavulanic acid (32.7%). The drugs with the best efficacy were tobramycin (96.4%), ciprofloxacin (92.6%) and tetracycline (90.9%). Multidrug resistance was observed in 23.5% of the analyzed strains. This research provides important information about the composition of the cloacal microbiota of wild birds in Mulungu, Brazil, as well as their health status. In addition, these results demonstrate that they harbor multidrug-resistant strains of Enterobacteriaceae.
A Simple Method to Dual Site-Specifically Label a Protein Using Tryptophan Auxotrophic Escherichia coli
Authors: Wu Ti , Joseph Simpson
Published: November 2021

Site-specifically labeling proteins with multiple dyes or molecular moieties is an important yet non-trivial task for many research, such as when using Föster resonance energy transfer (FRET) to study dynamics of protein conformational change. Many strategies have been devised, but usually done on a case-by-case basis. Expanded genetic code provided a general platform to incorporate non-canonical amino acids (ncAA), which can also enable multiple site-specific labeling, but it’s technically complicated and not suitable for some applications. Here we present a streamlined method that could enable dual site-specific protein labeling by using a tryptophan auxotroph of Escherichia coli to incorporate a naturally found tryptophan analog, 5-hydroxytryptophan into a recombinant protein. As a demonstration, we incorporated 5-hydroxytryptophan into E. coli release factor 1 (RF1), a protein known to possess two different conformations, and site-specifically attached two different fluorophores, one on 5-hydroxytryptophan and another on a cysteine residue. This method is simple, generally applicable, efficient, and can serve as an alternative way for researchers who want to install an additional labeling site in their proteins.
Chromosome splitting of Plasmodium berghei using the CRISPR/Cas9 system
Authors: Addo-Gyan Daniel , Matsushita Haruka , Sora Enya , Nishi Tsubasa , Yuda Masao , Shinzawa Naoaki , Iwanaga Shiroh
Published: November 2021

Spatial arrangement of chromosomes is responsible for gene expression in Plasmodium parasites. However, methods for rearranging chromosomes have not been established, which makes it difficult to investigate its role in detail. Here, we report a method for splitting chromosome in rodent malaria parasite by CRISPR/Cas9 system using fragments in which a telomere and a centromere were incorporated. The resultant split chromosomes segregated accurately into daughter parasites by the centromere. In addition, elongation of de novo telomeres were observed, indicating its proper function. Furthermore, chromosome splitting had no effect on development of parasites. Splitting of the chromosome is expected to alter its spatial arrangement, and our method will thus be useful for investigating its biological role related with gene expression.
Toward optimal fingerprint indexing for large scale genomics
Authors: Agret Clément , Cazaux Bastien , Limasset Antoine
Published: November 2021

Motivation

To keep up with the scale of genomic databases, several methods rely on local sensitive hashing methods to efficiently find potential matches within large genome collections. Existing solutions rely on Minhash or Hyperloglog fingerprints and require reading the whole index to perform a query. Such solutions can not be considered scalable with the growing amount of documents to index.

Results

We present NIQKI, a novel structure with well-designed fingerprints that lead to theoretical and practical query time improvements, outperforming state-of-the-art by orders of magnitude. Our contribution is threefold. First, we generalize the concept of Hyperminhash fingerprints in (h,m)-HMH fingerprints that can be tuned to present the lowest false positive rate given the expected sub-sampling applied. Second, we provide a structure able to index any kind of fingerprints based on inverted indexes that provide optimal queries, namely linear with the size of the output. Third, we implemented these approaches in a tool dubbed NIQKI that can index and calculate pairwise distances for over one million bacterial genomes from GenBank in a few days on a small cluster. We show that our approach can be orders of magnitude faster than state-of-the-art with comparable precision. We believe this approach can lead to tremendous improvements, allowing fast queries and scaling on extensive genomic databases.

Availability and implementation

We wrote the NIQKI index as an open-source C++ library under the AGPL3 license available at https://github.com/Malfoy/NIQKI. It is designed as a user-friendly tool and comes along with usage samples.

2012 ACM Subject Classification

Applied computing → Bioinformatics

Digital Object Identifier

10.4230/LIPIcs.WABI.2022.25
USPNet: unbiased organism-agnostic signal peptide predictor with deep protein language model
Authors: Chen Shenyang , Tan Qingxiong , Li Jingchen , Li Yu
Published: November 2021

Signal peptide is a short peptide located in the N-terminus of proteins. It plays an important role in targeting and transferring transmembrane proteins and secreted proteins to correct positions. Compared with traditional experimental methods to identify and discover signal peptides, the computational methods are faster and more efficient, which are more practical for the analysis of thousands or even millions of protein sequences in reality, especially for the metagenomic data. Therefore, computational tools are recently proposed to classify signal peptides and predict cleavage site positions, but most of them disregard the extreme data imbalance problem in these tasks. In addition, almost all these methods rely on additional group information of proteins to boost their performances, which, however, may not always be available. To deal with these issues, in this paper, we present Unbiased Organism-agnostic Signal Peptide Network (USPNet), a signal peptide prediction and cleavage site prediction model based on deep protein language model. We propose to use label distribution-aware margin (LDAM) loss and evolutionary scale modeling (ESM) embedding to handle data imbalance and object-dependence problems. Extensive experimental results demonstrate that the proposed method significantly outperforms all the previous methods on the classification performance. Additional study on the simulated metagenomic data further indicates that our model is a more universal and robust tool without dependency on additional group information of proteins, with the Matthews correlation coefficient improved by up to 17.5%. The proposed method will be potentially useful to discover new signal peptides from the abundant metagenomic data.
Genome Mining Uncovers Clustered Biosynthetic Pathways for Defense-Related Molecules in Bread Wheat
Authors: Polturak Guy , Dippe Martin , Stephenson Michael J , Misra Rajesh Chandra , Owen Charlotte , Ramirez-Gonzalez Ricardo , Haidioulis John , Schoonbeek Henk-Jan , Chartrain Laetitia , Borrill Philippa , Nelson David R , Brown James , Nicholson Paul , Uauy Cristobal , Osbourn Anne
Published: November 2021

Wheat is one of the most widely grown food crops in the world. However, it succumbs to numerous pests and pathogens that cause substantial yield losses. A better understanding of biotic stress responses in wheat is thus of major importance. Here we identify previously unknown pathogen-induced biosynthetic pathways that produce a diverse set of molecules, including flavonoids, diterpenes and triterpenes. These pathways are encoded by six biosynthetic gene clusters and share a common regulatory network. We further identify associations with known or novel phytoalexin clusters in other cereals and grasses. Our results significantly advance the understanding of chemical defenses in wheat and open up new avenues for enhancing disease resistance in this agriculturally important crop.
Genotype-specific transcriptional responses overshadow salinity effects in a marine diatom sampled along the Baltic Sea salinity cline
Authors: Pinseel Eveline , Nakov Teofil , Van den Berge Koen , Downey Kala M. , Judy Kathryn J. , Kourtchenko Olga , Kremp Anke , Ruck Elizabeth C. , Sjöqvist Conny , Töpel Mats , Godhe Anna , Alverson Andrew J.
Published: November 2021

The salinity gradient separating marine and freshwater environments represents a major ecological divide for microbiota, yet the mechanisms by which marine microbes have adapted to and ultimately diversified in freshwater environments are poorly understood. Here, we take advantage of a natural evolutionary experiment: the colonization of the brackish Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To understand how diatoms respond to low salinity, we characterized transcriptomic responses of S. marinoi grown in a common garden. Our experiment included eight genotypes from source populations spanning the Baltic Sea salinity cline. Changes in gene expression revealed a shared response to salinity across genotypes, where low salinities induced profound changes in cellular metabolism, including upregulation of carbon fixation and storage compound biosynthesis, and increased nutrient demand and oxidative stress. Nevertheless, the genotype effect overshadowed the salinity effect, as genotypes differed significantly in their response, both in the magnitude and direction of gene expression. Intraspecific differences included regulation of transcription and translation, nitrogen metabolism, cell signaling, and aerobic respiration. The high degree of intraspecific variation in gene expression observed here highlights an important but often overlooked source of biological variation associated with how diatoms respond and adapt to environmental change.
WITHDRAWN: KMT5C encodes robust heterochromatin retention and liquid-like behavior using limited sequence features
Authors: Strickfaden Hilmar , Missiaen Kristal , Knechtel Justin W. , Hendzel Michael J. , Underhill D. Alan
Published: November 2021

Withdrawal Statement

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2019/776625. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi:10.1101/776625.