bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of burden and segregation profiles of CNVs in patients with epilepsy
Authors: Moreau Claudia , Tremblay Frédérique , Wolking Stefan , Girard Alexandre , Laprise Catherine , Hamdan Fadi F. , Michaud Jacques L. , Minassian Berge A. , Cossette Patrick , Girard Simon L.
Published: February 2022

1

Objective

Microdeletions are associated with different forms of epilepsy but show incomplete penetrance, which is not well understood. We aimed to assess whether unmasked variants or double CNVs could explain incomplete penetrance.

Methods

We analyzed copy number variants (CNVs) in 603 patients with four different subgroups of epilepsy and 945 controls. CNVs were called from genotypes and validated on whole genome (WGS) or exome sequences (WES). CNV burden difference between patients and controls was obtained by fitting a logistic regression. CNV burden was assessed for small and large (> 1Mb) deletions and duplications and for deletions overlapping different genes set.

Results

Large deletions were enriched in genetic generalized epilepsies (GGE) compared to controls. We also found an enrichment of deletions in epilepsy genes and hotspots for GGE. We did not find truncating or functional variants that could have been unmasked by the deletions. We observed a double CNV hit in two patients. One patient also carried a de novo deletion in the 22q11.2 hotspot.

Interpretation

We could corroborate previous findings of an enrichment of large microdeletions and deletions in epilepsy genes in GGE. We could also replicate that microdeletions show incomplete penetrance. However, we could not validate the hypothesis of unmasked variants nor the hypothesis of double CNVs to explain the incomplete penetrance. We found a de novo hit on 22q11.2 that could be of interest. We also observed GGE families carrying a deletion on 15q13.3 hotspot that could be investigated in the Quebec founder population.
AGEAS: Automated Machine Learning based Genetic Regulatory Element Extraction System
Authors: Nakamoto Masayoshi , Tao Jiawang , Yu Jack
Published: February 2022

As rapid progress in sequencing technology since last decade, numerous mechanisms underlying cell functions and developmental processes have been revealed as complex regulations of gene expressions. Since single-cell RNA sequencing (scRNA-seq) made high-resolution transcriptomic view increasingly accessible, precise identification of gene regulatory network (GRN) describing cell types and cell states became achievable. However, extracting key regulatory elements, including gene regulatory pathways (GRPs), transcription factors (TFs), and targetomes, that accurately and completely reflects functionality changes in biological phenomena remains challenging. Herein, we describe AGEAS, an semi-supervised automated machine learning (AutoML) based genetic regulatory element extraction system that assesses importances of GRPs in resulting biological phenomena, such as cell type differentiation, physiological and pathological development, and reconstructs GRNs with extracted important GRPs for comprehensive inference. With several case studies in divergent research areas, we show that AGEAS can indeed extract informative regulatory elements and reconstruct networks to indicate regulatory changes in biological phenomena of interest.

Availability and implementation

The AGEAS code is available athttps://github.com/JackSSK/Ageas.
Diagnostic Ion Data Analysis Reduction (DIDAR) allows rapid quality control analysis and filtering of multiplexed single cell proteomics data
Authors: Jenkins Conor , Orsburn Benjamin C.
Published: February 2022

Recent advances in the sensitivity and speed of mass spectrometers utilized for proteomics and metabolomics workflows has led to a dramatic increase in data file size and density. For a field already challenged by data complexity due to a dependence on desktop PC architecture and the Windows operating systems, further compromises appear inevitable as data density scales. As one method to reduce data complexity, we present herein a light-weight python script that can rapidly filter and provide analysis metrics from tandem mass spectra based on the presence and number of diagnostic fragment ions determined by the end user. Diagnostic Ion Data Analysis Reduction (DIDAR) can be applied to any mass spectrometry dataset to create smaller output files containing only spectra likely to contain post-translational modifications or chemical labels of interest. In this study we describe the application DIDAR within the context of multiplexed single cell proteomics workflows. When applied in this manner using reporter fragment ions as diagnostic signatures, DIDAR can provide quality control metrics based on the presence of reporter ions derived from single human cells and simplified output files for search engine analysis. The simple output metric text files can be used to rapidly flag entire LCMS runs with technical issues and remove them from downstream analysis based on end user minimum requirements. Acquisition files that pass these criteria are further improved through the automatic removal of spectra where insufficient signal from single cells is observed. We describe the application of DIDAR to two recently described multiplexed single cell proteomics datasets.

Abstract Graphic
Single-Case Disconnectome Lesion-symptom Mapping: Identifying Two Subtypes of Limb Apraxia
Authors: Metzgar Rachel , Stoll Harrison , Grafton Scott T. , Buxbaum Laurel J. , Garcea Frank E.
Published: February 2022

Influential theories of skilled action posit that distinct cognitive mechanisms and neuroanatomic substrates support meaningless gesture imitation and tool use pantomiming, and poor performance on these tasks are hallmarks of limb apraxia. Yet prior research has primarily investigated brain-behavior relations at the group level; thus, it is unclear whether we can identify individuals with isolated impairments in meaningless gesture imitation or tool use pantomiming whose performance is associated with a distinct neuroanatomic lesion profile. The goal of this study was to test the hypothesis that individuals with disproportionately worse performance in meaningless gesture imitation would exhibit cortical damage and white matter disconnection in left fronto-parietal brain regions, whereas individuals with disproportionately worse performance in tool use pantomiming would exhibit cortical damage and white matter disconnection in left temporo-parietal brain regions. Fifty-eight participants who experienced a left cerebrovascular accident took part in a meaningless gesture imitation task, a tool use pantomiming task, and a T1 structural MRI. Two participants were identified who had relatively small lesions and disproportionate impairments on one task relative to the other, as well as below-control-level performance on one task and not the other. Using these criteria, one participant was disproportionately impaired at meaningless gesture imitation, and the other participant was disproportionately impaired at pantomiming tool use. Graph theoretic analysis of each participant’s structural disconnectome demonstrated that disproportionately worse meaningless gesture imitation performance was associated with disconnection among the left inferior parietal lobule, the left superior parietal lobule, and the left middle and superior frontal gyri, whereas disproportionately worse tool use pantomiming performance was associated with disconnection between left temporal and parietal regions. Our results demonstrate that relatively focal lesions to specific portions of the Tool Use Network can be associated with distinct limb apraxia subtypes.

Highlights

Distinct subtypes of apraxia are supported by distinct neuroanatomic substrates.

Fronto-parietal lesions are associated with meaningless imitation deficits.

Temporo-parietal lesions are associated with tool use pantomiming deficits.

Structural connectivity among cortical areas supports a distributed praxis system.
The gene signatures of human alpha cells in types 1 and 2 diabetes indicate disease-specific pathways of alpha cell dysfunction
Authors: Bosi Emanuele , Marchetti Piero , Rutter Guy A. , Eizirik Decio L.
Published: February 2022

Glucagon secretion is perturbed in both type 1 and type 2 diabetes (T1D, T2D) the pathophysiological changes at the level of individual pancreatic alpha cells are still largely obscure. Using recently-curated single-cell RNA data from human donors with either T1D or T2D and appropriate controls, we leveraged alpha cell transcriptomic alterations consistent with both common and discrete pathways. Firstly, altered expression of genes associated with alpha cell identity (ARX, MAFB) was common to both diseases. In contrast, increased expression of cytokine-regulated genes and genes involved in glucagon biosynthesis and processing were apparent in T1D, whereas mitochondrial genes associated with reactive oxygen species generation (COX7B, NQO2) were dysregulated in alpha cells from T2D patients. Conversely, T1D alpha cells displayed alterations in genes associated with autoimmune-induced ER stress (ERLEC1, HSP90) whilst those from T2D patients showed changes in glycolytic and citrate cycle genes (LDH, PDHB, PDK4) which were unaffected in T1D. These findings suggest that despite some similarities related to loss-of-function, the alterations of alpha cells present important disease-specific signatures, suggesting that they are secondary to the main pathogenic events characteristic to each disease, namely immune-mediated-or metabolic-mediated-stress in respectively T1D and T2D.
The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability
Authors: Wischnewski Miles , Haigh Zachary J. , Shirinpour Sina , Alekseichuk Ivan , Opitz Alexander
Published: February 2022

Neural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8-13 Hz) and beta (14-30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown. Here, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0°, 90°, 180°, and 270°) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study. Mixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations. Our results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.
Ribosome profiling reveals the translational landscape and allele-specific translation efficiency in rice
Authors: Zhu Xi-Tong , Zhou Run , Che Jian , Zheng Yu-Yu , Qamar Muhammad Tahir ul , Feng Jia-Wu , Zhang Jianwei , Gao Junxiang , Chen Ling-Ling
Published: February 2022

Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs. Many studies have revealed the translational regulation in plants in response to various environmental stimuli. However, there has been no comprehensive landscape of translational regulation and allele-specific translation efficiency in multiple tissues of plants, especially in rice, a main staple crop feeding nearly half of the world population. Here, we used RNA-seq and Ribo-seq data to analyze the transcriptome and translatome of an elite hybrid rice SY63 and its parental varieties ZS97 and MH63. The results revealed that gene expression patterns varied more significantly between tissues than between varieties at both transcriptional and translational levels. Besides, we identified 3,392 upstream open reading frames (uORFs), and most of the uORF-containing genes were enriched for transcription factors. Only 668 long non-coding RNAs could be translated into peptides. Finally, we discovered numerous genes with allele-specific translation efficiency in SY63, and further demonstrated that somecis-regulatory elements (secondary structures of mRNAs and the binding of miRNAs) may contribute to allelic divergence in translation efficiency. Overall, our findings may improve the understanding of translational regulation in rice and provide information for the molecular basis of breading research.
Neprosin belongs to a new family of glutamic peptidase based on in silico evidence
Authors: Ting Tiew-Yik , Baharin Anis , Ramzi Ahmad Bazli , Ng Chyan-Leong , Goh Hoe-Han
Published: February 2022

Neprosin was first discovered in the insectivorous tropical pitcher plants of Nepenthes species as a novel protease with prolyl endopeptidase (PEP) activity. Neprosin has two uncharacterized domains of neprosin activation peptide and neprosin. A previous study has shown neprosin activity in hydrolyzing proline-rich gliadin, a gluten component that triggers celiac disease. In this study, we performed in silico structure-function analysis to investigate the catalytic mechanism of neprosin. Neprosin sequences lack the catalytic triad and motifs of PEP family S9. Protein structures of neprosins from Nepenthes × ventrata (NvNpr) and N. rafflesiana (NrNpr1) were generated by ab initio methods and comparatively assessed to obtain high-quality models. Structural alignment of models to experimental structures in the Protein Data Bank (PDB) found a high structural similarity to glutamic peptidases. Further investigations reveal other resemblances to the glutamic peptidases with low optimum pH that activates the enzyme via autoproteolysis for maturation. Two highly conserved glutamic acid residues, which are stable according to the molecular dynamics simulation, can be found at the active site of the substrate cleft. Protein docking demonstrated that mature neprosins bind well with potent antigen αI-gliadin at the putative active site. Taken together, neprosins represent a new glutamic peptidase family, with a putative catalytic dyad of two glutamic acids. This study illustrates a hypothetical enzymatic mechanism of the neprosin family and demonstrates the useful application of an accurate ab initio protein structure prediction in the structure-function study of a novel protein family.
Negative Impact of Daily Screen Use on Inhibitory Control Network in Preadolescence: A Two-Year Follow-Up Study
Authors: Chen Ya-Yun , Yim Hyungwook , Lee Tae-Ho
Published: February 2022

The COVID-19 pandemic has made an unprecedented shift in children’s daily lives. Children are increasingly spending time with screens to learn and connect with others. As the online environment rapidly substitutes in-person experience, understanding children’s neuropsychological trajectories associated with screen experiences is important. Previous findings suggest that excessive screen use can lead children to prefer more immediate rewards over delayed outcomes. We hypothesized that increased screen time delays a child’s development of inhibitory control. By analyzing neuropsychological data from 8,324 children (9-11ys) from the ABCD Study, we found that children who had more screen time showed a higher reward orientation and a weaker inhibitory control system (i.e., fronto-striatal circuitry) in the brain. Importantly, we found that the interaction between screen exposure and reward sensitivity negatively influenced the development of the inhibitory control system in the brain over a two year period. These results indicate possible negative long-term impacts of increased daily screen time on children’s neuropsychological development. The results further demonstrated that screen time influences dorsal striatum connectivity, which suggests that the effect of daily screen use is a habitual seeking behavior. The study provides neural and behavioral evidence on the negative impact of daily screen use on developing children.
Quantitative Evaluation of Nonlinear Methods for Population Structure Visualization & Inference
Authors: Ubbens Jordan , Feldmann Mitchell J. , Stavness Ian , Sharpe Andrew G.
Published: February 2022

Population structure (also called genetic structure and population stratification) is the presence of a systematic difference in allele frequencies between sub-populations in a population as a result of non-random mating between individuals. It can be informative of genetic ancestry, and in the context of medical genetics it is an important confounding variable in genome wide association studies. Recently, many nonlinear dimensionality reduction techniques have been proposed for the population structure visualization task. However, an objective comparison of these techniques has so far been missing from the literature. In this paper, we discuss the previously proposed nonlinear techniques and some of their potential weaknesses. We then propose a novel quantitative evaluation methodology for comparing these nonlinear techniques, based on populations for which pedigree is either known a-priori through artificial selection or simulation. Based on this evaluation metric, we find graph-based algorithms such as t-SNE and UMAP to be superior to PCA, while neural network based methods fall behind.
In vivodetection of substantia nigra and locus coeruleus volume loss in Parkinson’s disease using neuromelanin-sensitive MRI: Replication in two cohorts
Authors: Hwang Kristy S. , Langley Jason , Tripathi Richa , Hu Xiaoping P. , Huddleston Daniel E.
Published: February 2022

Patients with Parkinson’s disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinson’s disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinson’s disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology.

Two separate cohorts of Parkinson’s disease patients and controls were recruited from the Emory Movement Disorders Clinic and scanned on two different MRI scanners. In cohort 1, imaging data from 19 controls and 22 Parkinson’s disease patients were acquired with a Siemens Trio 3 Tesla scanner using a 2D gradient echo sequence with magnetization transfer preparation pulse. Cohort 2 consisted of 33 controls and 39 Parkinson’s disease patients who were scanned on a Siemens Prisma 3 Tesla scanner with a similar imaging protocol. Locus coeruleus and substantia nigra pars compacta volumes were segmented in both cohorts.

Substantia nigra pars compacta volume (Cohort 1:p=0.0148; Cohort 2:p=0.0011) and locus coeruleus volume (Cohort 1:p=0.0412; Cohort 2:p=0.0056) were significantly reduced in the Parkinson’s disease group as compared to controls in both cohorts. This imaging approach robustly detects Parkinson’s disease effects on these structures, indicating that it is a promising marker for neurodegenerative neuromelanin loss.
When mistrust in the government and scientists reinforce social inequalities in vaccination against Covid-19
Authors: Bajos Nathalie , Spire Alexis , Silberzan Léna , Sireyjol Antoine , Jusot Florence , Meyer Laurence , Franck Jeanna-Eve , Warszawski Josiane ,   the EpiCov study group
Published: February 2022

Objective

To assess whether mistrust in the government and scientists reinforces social and racial inequalities in vaccination practises

Design

A follow-up of a random population-based cohort survey.

Setting

In July 2021, in France.

Participants

80,971 participants aged 18 years and more.

Main outcome measures

Adjusted odds ratios of Covid-19 vaccination status (received at least one dose/ intends to get vaccinated/ does not know whether to get vaccinated/refuses vaccination) were assessed using multinomial regressions to test associations with social and mistrust factors and to study how these two factors interacted with each other.

Results

In all, 72.2% were vaccinated at the time of the survey. The population of unvaccinated people was younger, less educated, had lower incomes, and more often belonged to racialised minorities, as compared to vaccinated people. Mistrust of government and scientists to curb the spread of the epidemic were the factors most associated with refusing to be vaccinated: OR=8.86 (7.13 to 11.00) for the government and OR=9.07 (7.71 to 10.07) for scientists, compared to vaccinated people. Mistrust was more prevalent among the poorer which consequently reinforced social inequalities in vaccination. The 10% poorest who did not trust the government reached an OR of 16.2 (11.9 to 22) for refusing to be vaccinated compared to the 10% richest who did.

Conclusion

There is a need to develop depoliticised outreach programmes targeted at the most socially disadvantaged groups, and to design vaccination strategies conceived with people from different social and racial backgrounds to enable them to make fully informed choices.
Trajectories of Perceived Negative Impact in Parents of Individuals with Autism Spectrum Disorders from 9 to 25 years of age
Authors: Christopher Kourtney , Elias Rebecca , Lord Catherine
Published: February 2022

Caregivers raising a child with autism experience increased parental burden, though many have positive experiences as well. Perceived negative impact, a form of parental burden, is the degree to which a caregiver reports negative financial, social, and emotional experiences associated with having a child with a disability. This longitudinal study defined parental perceived negative impact trajectory classes across time, determined predictors, and explored the relationship between functional adult outcomes and impact class. Participants (n = 209) were comprised of caregivers whose child received an ASD diagnosis or had developmental delay. Latent class growth modeling defined three trajectory classes (e.g., low [n = 68, 32.54%], medium [n = 98, 46.89%], and high [n = 43, 20.57%]). Regressions revealed the low impact trajectory class had more caregivers who were racial minorities, less educated, and more socially supported. Membership in the high negative impact class was associated with increased childhood hyperactivity, irritability, autism symptomology, and poor adaptive skills. The low negative impact trajectory class was associated with young adults achieving more functional outcomes. Overall negative impact declined over time all for all classes, though never completely subsided. Possible implications for clinical practices are discussed
Demographic and socioeconomic factors predict maternal postpartum rehospitalization: a retrospective nuMoM2b dataset study
Authors: Wakefield Colin , Frasch Martin G
Published: February 2022

The advent of artificial intelligence/machine learning (AI/ML) in medicine has opened opportunities for harnessing the power of ML to predict patient outcomes based on diverse data contained in the electronic medical records (EMR). Taken by themselves singular features represented by such diverse data are often not clearly predictive but combined in an ML modeling framework such so-called weak learners have the power to yield highly predictive models of health outcomes. We hypothesized that sociodemographic and basic, easily obtainable health characteristics of pregnant mothers strongly predict the risk of rehospitalization. Using the nuMoM2b dataset from NICHD and reproducible, open access AI/ML techniques we tested and validated this hypothesis. Among a large (n=10,038) and geographically diverse cohort of nulliparous women with singleton gestations, the present findings show that while some of these characteristics highlight the known disparities in health outcomes (race/ethnicity), most of them are modifiable through social policies and health counseling. These include access to and support during education, comprehensive health insurance, alleviating coming out of poverty, smoking, and unhealthy lifestyle habits. Across the four ML models deployed, the results are mutually reinforcing yielding a clear cohesive picture. This solution can be used to develop a prospective risk prediction for this important health outcome in pregnant mothers. The strengths of the presented solution are its focus on preventable maternal morbidities and risk factors, demonstration of the impact on adversely affected populations, and reproducible step-by-step executable, documented open-access code with relatively low computational requirements. This enables easy adoption and further development on this and other similar datasets to study the contributions and predictive power of various factors to maternal morbidities.
Domestication and lowland adaptation of coastal preceramic maize from Paredones, Peru
Authors: Vallebueno-Estrada Miguel , Hernández-Robles Guillermo G. , González-Orozco Eduardo , López-Valdivia Iván , Tham Teresa Rosales , Sánchez Víctor Vásquez , Swarts Kelly , Dillehay Tom D. , Vielle-Calzada Jean-Philippe , Montiel Rafael
Published: February 2022

Archaeological cobs from Paredones and Huaca Prieta (Peru) are phenotypically indistinguishable from modern maize. This contrasts with the earliest Mexican macro-specimens from Guila Naquitz and San Marcos, which are phenotypically intermediate even though they date more recently in time. These observations suggest at least two alternative scenarios, one in which maize was domesticated earlier than previously thought in the lowland Mesoamerica, followed by rapid lowland dispersal to Peru, and another in which maize was independently domesticated in South America and subsequently lost, as current evidence supports a single origin for all modern maize. To gain insights into the origins of ancient Peruvian maize, we sequenced DNA from three Paredones specimens dating 6775 to 5000 calibrated years before present (BP) and conducted comparative analyses with two teosinte subspecies (Zea maysssp.mexicanaandparviglumis) and extant maize, including highland and lowland landraces from Mesoamerica and South America. We show that Paredones maize originated from the same domestication event as Mexican maize and was domesticated by 6775 BP, implying rapid dispersal followed by improvement. Paredones maize show minimal levels of gene flow frommexicana, smaller than those observed in teosinteparviglumis. It also harbors significantly fewer alleles previously found to be adaptive to highlands, but not of alleles adaptive to lowlands, supporting a lowland migration route. Our overall results imply that Paredones maize originated in Mesoamerica, arrived in Peru withoutmexicanaintrogression through a rapid lowland migration route, and underwent improvements in both Mesoamerica and South America.

Significance Statement

The coastal Peruvian preceramic sites of Paredones and Huaca Prieta provide the earliest known maize macro-remains. Found more than 3,800 km away from the maize center of origin and presenting a phenotypically modern cob constitution relative to their antiquity, these specimens represent a paradox for understanding maize evolution and dispersal. We show that Paredones maize originated in Mesoamerica, like all known maize, and arrived in South America without introgression from the teosintemexicana. Since modern maize has substantial contributions frommexicana, it raises the question of whenmexicanaintrogression spread to South America. Paredones maize preferentially shares adaptive allelic diversity with lowland Mesoamerican samples, suggesting a migration route probably associated with a coastal corridor previously identified with archeological findings.
Age influences audiovisual speech processing in multi-talker scenarios – Evidence from cortical oscillations
Authors: Begau Alexandra , Klatt Laura-Isabelle , Schneider Daniel , Wascher Edmund , Getzmann Stephan
Published: February 2022

Age-related differences in the processing of audiovisual speech in a multi-talker environment were investigated analyzing event-related spectral perturbations (ERSPs), focusing on theta, alpha, and beta oscillations that are assumed to reflect conflict processing, multisensory integration, and attentional mechanisms, respectively. Eighteen older and 21 younger healthy adults completed a two-alternative forced-choice word discrimination task, responding to audiovisual speech stimuli. In a cocktail-party scenario with two competing talkers (located at-15° and 15° azimuth), target words (/yes/ or /no/) appeared at a pre-defined (attended) position, distractor words at the other position. In two audiovisual conditions, acoustic speech was combined either with congruent or uninformative visual speech. While a behavioral benefit for congruent audiovisual speech occurred for both age groups, differences between audiovisual conditions in the theta and beta band were only present for older adults. A stronger increase in theta perturbations for stimuli containing uninformative visual speech could be associated with early conflict processing, while a stronger suppression in beta perturbations for congruent audiovisual speech could be associated to audiovisual integration. Compared to the younger group, the older group showed generally stronger beta perturbations. No condition differences in the alpha band were found. Overall, the findings suggest age-related differences in audiovisual speech integration in a multi-talker environment. While the behavioral benefit of congruent audiovisual speech was unaffected by age, older adults had a stronger need for cognitive control when processing conflicting audiovisual speech input. Furthermore, mechanisms of audiovisual integration are differently activated depending on the informational content of the visual information.
Chloroplast genome assemblies and comparative analyses of major Vaccinium berry crops
Authors: Fahrenkrog Annette M. , Matsumoto Gabriel , Toth Katalin , Jokipii-Lukkari Soile , Salo Heikki M. , Häggman Hely , Benevenuto Juliana , Munoz Patricio
Published: February 2022

Background

Vaccinium is an economically important genus of berry crops in the family Ericaceae. Given the numerous hybridizations and polyploidization events among Vaccinium species, the taxonomy of this genus has remained uncertain and the subject of long debate. Therefore, the availability of more genomic resources for Vaccinium can provide useful tools for phylogenetic resolution, species identification, authentication of berry food products, and a framework for genetic engineering.

Results

In this study, we assembled five Vaccinium chloroplast sequences representing the following berry types: northern highbush blueberry (V. corymbosum), southern highbush blueberry (V. corymbosum hybrids), rabbiteye blueberry (V. virgatum), lowbush blueberry (V. angustifolium), and bilberry (V. myrtillus). Two complete plastid genomes were achieved using long-read PacBio sequencing, while three draft sequences were obtained using short-read Illumina sequencing. Comparative analyses also included other previously available Vaccinium chloroplast sequences, especially the commercially important species V. macrocarpon (cranberry). The Vaccinium chloroplast genomes exhibited a circular quadripartite structure, with an overall highly conserved synteny and sequence identity among them. Despite their high similarity, we identified some polymorphic regions in terms of expansion/contraction of inverted repeats, gene copy number variation, simple sequence repeats, and single nucleotide polymorphisms. Phylogenetic analysis revealed multiple origins of highbush blueberry plastomes, likely due to the hybridization events during northern and southern highbush blueberry domestication.

Conclusions

Our results enrich the genomic data availability for new Vaccinium species by sequencing and assembling the chloroplast DNA of major economically important berry types. Additional whole plastome analyses including more samples and wild species will be useful to obtain a refined knowledge of the maternal breeding history of blueberries and increase phylogenetic resolution at low taxonomic levels.
Inhibitory effect of EGCG-AgNPs and their lysozyme bioconjugates on biofilm formation and cytotoxicity
Authors: Meesaragandla Brahmaiah , Hayet Shahar , Fine Tamir , Janke Una , Chai Liraz , Delcea Mihaela
Published: February 2022

Biofilms are multicellular communities of microbial cells that grow on natural and synthetic surfaces. They have become the major cause for hospital-acquired infections because once they form, they are very difficult to eradicate. Nanotechnology offers a new approach to fight biofilm-associated infections. Here, we report on the synthesis of silver nanoparticles (AgNPs) with antibacterial ligand epigallocatechin gallate (EGCG) and the formation of lysozyme protein corona on AgNPs as shown by UV-Vis, dynamic light scattering, and circular dichroism analyses. We further tested the activity of EGCG-AgNPs and their lysozyme bioconjugates on the viability of Bacillus subtilis cells and biofilm formation. Our results showed that, although EGCG-AgNPs presented no antibacterial activity on planktonic Bacillus subtilis cells, they inhibited B. subtilis biofilm formation at concentrations larger than 40 nM and EGCG-AgNP-lysozyme bioconjugates inhibited biofilms at concentrations above 80 nM. Cytotoxicity assays performed with human cells showed a reverse trend, where EGCG-AgNPs barely affected human cell viability, while EGCG-AgNP-lysozyme bioconjugates severely hampered viability. Our results therefore demonstrate that EGCG-AgNPs may be used as non-cytotoxic antibiofilm agents.
Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors
Authors: Atsumi Nanako , Yasumatsu Keiko , Takashina Yuriko , Ito Chiaki , Yasui Norihisa , Margolskee Robert F. , Yamashita Atsuko
Published: February 2022

Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl−is thought to participate in taste sensation through an unknown mechanism. Here we describe Cl−ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl−binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl−binding induced a conformational change in T1r2a/T1r3LBD at sub-to low-mM concentrations similar to canonical taste substances. Furthermore, oral Cl−application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl−evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration.
Dynamic genetic adaptation of Bacteroides thetaiotaomicron murine gut colonization
Authors: Zhang Manjing , Kennedy Megan , DeLeon Orlando , Bissell Jacie , Trigodet Florian , Lolans Karen , Temelkova Sara , Carroll Katherine T. , Fiebig Aretha , Deutschbauer Adam , Sidebottom Ashley M. , Henry Chris , Rice Phoebe A. , Bergelson Joy , Chang Eugene B.
Published: February 2022

To understand how a bacterium ultimately succeeds or fails in adapting to a new environment, it is essential to assess the temporal dynamics of its fitness over the course of colonization. The mammalian gut, into which exogenous microorganisms are regularly introduced, represents a biologically and clinically relevant system to explore microbial adaptational processes. In this study, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron, into the guts of germ-free mice to 1) determine whether the genetic requirements for colonization shift over time and, if so, 2) characterize the biological functions required for microbial survival at different points of colonization. The results of a high-throughput functional genetics assay (BarSeq), transcriptomics, and metabolomics converge on several conclusions. First, adaptation to the host gut occurs in distinct stages. We observed drastic changes in gene usage during the first week, shifting from high expression of amino acid biosynthesis to polysaccharide utilization genes. These changes were sustained thereafter, except for the continued upregulation of a single polysaccharide utilization locus responsible for the degradation of raffinose-family oligosaccharides rich in the standard chow diet fed to our mice. Spontaneous mutations in wildtype Bt also evolve around this locus, highlighting the importance of efficient carbohydrate metabolism in long-term persistence within a monoassociated gut. To improve microbiome-based therapies, it will be important to appreciate and meet the distinct needs of the organism during each stage of colonization.

Importance

Microbes regularly disperse across and adapt to new environments and ecological niches. A clinically significant microbial niche home to trillions of microbes is the mammalian gut. Temporal processes of microbial adaptation over the course of gut colonization are poorly understood on a genetic, transcriptional, and metabolite level. In this study, we leverage a three-pronged approach to characterize gut colonization as a dynamic process with shifting genetic determinants of microbial fitness. This study sheds light on host colonization by Bacteroides thetaiotaomicron, an organism that is prevalent and dominant across healthy human microbiomes, and not only identifies key pathways involved in colonization, but determines the timing of when these pathways are most vital to colonization success. By demonstrating that the key determinants of colonization success in the gut change over time, the results of this study highlight the importance of considering ecological dynamics in developing more effective microbiome-based therapies.
Autonomic dysfunction is associated with the development of arterial stiffness: The Whitehall II cohort
Authors: Schaarup Jonas , Christensen Martin S. , Hulman Adam , Hansen Christian Stevns , Vistisen Dorte , Tabák Adam G. , Witte Daniel R. , Bjerg Lasse
Published: February 2022

Background and aim

To examine the association between baseline level and change of autonomic nervous function with subsequent development of arterial stiffness.

Methods

Autonomic nervous function was assessed of 4,901 participants of the Whitehall II occupational cohort by heart rate variability (HRV) indices and resting heart rate (rHR) three times between 1997-2009, while arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measured twice between 2007-2013. First, individual HRV/rHR levels and annual changes were estimated. Then, we modelled the development of PWV by HRV/rHR using linear mixed effect models. First, we adjusted for sex and ethnicity (model 1), and then for socioeconomic and lifestyle factors, various clinical measurements, and medications (model 2).

Results

A decrease in HRV and unchanged rHR was associated with subsequent higher levels of PWV, but the effect of a change in HRV was less pronounced at higher ages. A typical individual aged 65 years with a SDNN level of 30 ms and a 2% annual decrease in SDNN had 1.32 (0.95; 1.69) higher PWV compared to one with the same age and SDNN level but with a 1% annual decrease in SDNN. Further adjustment had no major effect on the results.

Conclusion

People who experience a steeper decline of autonomic nervous function have higher levels of arterial stiffness. However, the association was weaker at higher ages.
Epigenetic aging and perceived psychological stress in old age
Authors: Vetter Valentin Max , Drewelies Johanna , Sommerer Yasmine , Kalies Christian Humberto , Regitz-Zagrosek Vera , Bertram Lars , Gerstorf Denis , Demuth Ilja
Published: February 2022

Adverse effects of psychological stress on physical and mental health, especially in older age, are well documented. How perceived stress relates to the epigenetic clock measure, DNA methylation age acceleration (DNAmAA), is less well understood and existing studies reported inconsistent results.

DNAmAA was estimated from five epigenetic clocks (7-CpG, Horvath’s, Hannum’s, PhenoAge and GrimAge DNAmAA). Cohen’s Perceived Stress Scale (PSS) was used as marker of psychological stress.

We analyzed data from 1,100 Berlin Aging Study II (BASE-II) participants assessed as part of the GendAge study (mean age = 75.6 years, SD = 3.8 years, 52.1% women).

In a first step, we replicated well-established associations of perceived stress with morbidity, frailty, and symptoms of depression in the BASE-II cohort studied here. In a second step, we did not find any statistically significant association of perceived stress with any of the five epigenetic clocks in multiple linear regression analyses that adjusted for covariates.

Although the body of literature suggests an association between higher DNAmAA and stress or trauma during early childhood, the current study found no evidence for an association of perception of stress with DNAmAA in older people. We discuss possible reasons for the lack of associations and highlight directions for future research.
Female gender, depressive symptoms, manual job, and higher physical disability predict long term low back pain persistence
Authors: Gomes Luís Antunes , Rodrigues Ana Maria , Branco Jaime C. , Canhão Helena , Cruz Eduardo Brazete
Published: February 2022

Background

Low Back Pain (LBP) is a long-term health condition with distinct clinical courses. The characterization of these courses together with the identification of prognostic factors of a persistent disabling LBP course has the potential to enable a better identification of patients in high-risk and ultimately allow the development of personalized interventions to change their long-term prognosis. This study aimed to assess the course of chronic LBP (CLBP) over 5 years in a large population-based study, its cumulative impact on disability and health-related quality of life (HRQoL) and the indicators for persistent CLBP course.

Material and methods

Active CLBP participants were identified from a representative sample of 10.661 adults randomly recruited from the dwelling population of EpiDoC. Pain, disability and HRQoL were assessed at three time-points. According to their pain symptoms over time, participants were classified as having a persistent or relapsing pain course. A General Linear Model was used to compare mean differences between and within groups. The relation between baseline variables and persistent CLBP was modulated through logistic regression.

Results

Among the 1.201 adults with active CLBP at baseline, 634 completed the three time-points of data collection (52.8%) and 400 (63.1%) were classified as having a persistent course. Statistically significant interactions were found between the group and time on disability (F (2.126)= 23.78, p<0.001) and HRQoL (F (2.125)= 82.78, p<0.001). In the adjusted model, the persistent course was associated with the disability level (OR: 1.84, CI95% 1.4 to 2.4), presence of depressive symptoms (OR: 1.96, CI95% 1.2 to 3.2), female gender (OR: 1.9, CI95% 1.26-2.87), and having a manual job (OR: 1.46, CI95% 1.02 to 2.1).

Conclusion

In the long-term, CLBP patients have distinct clinical courses. Being female, presenting depressive symptoms, having a manual job and a higher disability at baseline predict a CLBP persistent outcome.
A central protein complex essential for Invasion inToxoplasma gondii
Authors: Singer Mirko , Simon Kathrin , Forné Ignasi , Meissner Markus
Published: February 2022

Apicomplexa are obligate intracellular parasites. While most species are restricted to specific hosts and cell types,Toxoplasma gondiican invade every nucleated cell derived from warm-blooded animals. This broad host range suggests that this parasite can recognize multiple host cell ligands or structures, leading to the activation of a central protein complex, which should be conserved in all apicomplexans. During invasion, the unique secretory organelles (micronemes and rhoptries) are sequentially released and several micronemal proteins have been suggested to be required for host cell recognition and invasion. However, to date only few micronemal proteins have been demonstrated to be essential for invasion.

Cysteine Repeat Modular Proteins (CRMPs) are a family of apicomplexan specific proteins. In Toxoplasma gondii, two CRMPs are present in the genome. The Kringle domain containing protein (CRMPA) and the GCC2 GCC3 domain containing protein (CRMPB). Here we demonstrate that both proteins form a complex that contains additional micronemal proteins. Disruption of this complex results in a block of rhoptry secretion and parasites being unable to invade the host cell. In conclusion, this complex is a central invasion complex conserved in all apicomplexans.
Tropical hummingbird pollination networks are resistant to short-term experimental removal of a common flowering plant
Authors: Leimberger Kara G. , Hadley Adam S. , Frey Sarah J.K. , Betts Matthew G.
Published: February 2022

Theory predicts that the structure of plant-pollination networks should withstand disturbance, but experiments testing this prediction remain uncommon. In this study, we simulated the local extinction of a hummingbird-pollinated understory plant,Heliconia tortuosa, from tropical forest fragments using a replicated Before-After-Control-Impact design while quantifying hummingbird abundance and space use (383 hummingbird captures and 72 radio-tagged individuals), floral visitation rates (>19,000 observation hours), and pollination success (529 flowers). We expected thatH. tortuosaremoval would either result in (i) network collapse, in which hummingbirds vacate fragments and compromise the reproductive success of other flowering plants, or (ii) increased hummingbird reliance on alternative resources (rewiring), leading to sustained fragment use. In our experiment, hummingbird behavior and pollination were remarkably resistant to loss ofH. tortuosa, a locally common plant species representing 30-40% of the available nectar resources on average. The exact mechanisms enabling short-term hummingbird persistence after resource removal remain unclear, as we did not discover evidence of rewiring. We hypothesize that physiological adaptations (e.g., torpor and insectivory) may have allowed hummingbird persistence, perhaps alongside high movement ability. With the important caution that short-term experiments may not emulate natural extinction processes, our study provides support for predictions that pollination networks may be robust to plant species loss.