bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-optimized feeding is beneficial without enforced fasting
Authors: Kelly Kevin P. , Ellacott Kate L. J. , Chen Heidi , McGuinness Owen P. , Johnson Carl Hirschie
Published: October 2021

Time-restricted feeding (TRF) studies underscore that
when
food is consumed during the daily cycle is important for weight gain/loss because the circadian clock rhythmically modulates metabolism. However, the interpretation of previous TRF studies has been confounded by study designs that introduced an extended period of enforced fasting. We introduce a novel time-optimized feeding (TOF) regimen that disentangles the effects of phase-dependent feeding from the effects of enforced fasting in mice, as well as providing a laboratory feeding protocol that more closely reflects the eating patterns of humans who usually have 24 hour access to food. Moreover, we test whether a sudden switch from ad libitum food access to TRF evokes a corticosterone (stress) response. Our data indicate that the timing of high-fat feeding under TOF allows most of the benefit of TRF without obligatory fasting or evoking a stress response. This benefit occurs through stable temporal coupling of carbohydrate/lipid oxidation with feeding. These results highlight that timing the ingestion of calorically dense foods to optimized daily phases will enhance lipid oxidation and thereby limit fat accumulation.
Intrinsically disordered proteins: modes of binding with emphasis on disordered domains
Authors: Morris Owen Michael , Torpey James Hilary , Isaacson Rivka Leah
Published: October 2021

Our notions of protein function have long been determined by the protein structure–function paradigm. However, the idea that protein function is dictated by a prerequisite complementarity of shapes at the binding interface is becoming increasingly challenged. Interactions involving intrinsically disordered proteins (IDPs) have indicated a significant degree of disorder present in the bound state, ranging from static disorder to complete disorder, termed ‘random fuzziness’. This review assesses the anatomy of an IDP and relates how its intrinsic properties permit promiscuity and allow for the various modes of interaction. Furthermore, a mechanistic overview of the types of disordered domains is detailed, while also relating to a recent example and the kinetic and thermodynamic principles governing its formation.
Combining epidemiological and ecological methods to quantify social effects on
Escherichia coli
transmission
Authors: Farthing Trevor S. , Dawson Daniel E. , Sanderson Mike W. , Seger Hannah , Lanzas Cristina
Published: October 2021

Enteric microparasites like
Escherichia coli
use multiple transmission pathways to propagate within and between host populations. Characterizing the relative transmission risk attributable to host social relationships and direct physical contact between individuals is paramount for understanding how microparasites like
E. coli
spread within affected communities and estimating colonization rates. To measure these effects, we carried out commensal
E. coli
transmission experiments in two cattle (
Bos taurus
) herds, wherein all individuals were equipped with real-time location tracking devices. Following transmission experiments in this model system, we derived temporally dynamic social and contact networks from location data. Estimated social affiliations and dyadic contact frequencies during transmission experiments informed pairwise accelerated failure time models that we used to quantify effects of these sociobehavioural variables on weekly
E. coli
colonization risk in these populations. We found that sociobehavioural variables alone were ultimately poor predictors of
E. coli
colonization in feedlot cattle, but can have significant effects on colonization hazard rates (
p
≤ 0.05). We show, however, that observed effects were not consistent between similar populations. This work demonstrates that transmission experiments can be combined with real-time location data collection and processing procedures to create an effective framework for quantifying sociobehavioural effects on microparasite transmission.
Prediction model for aerodynamic coefficients of iced quad bundle conductors based on machine learning method
Authors: Mou Zheyue , Yan Bo , Yang Hanxu , Cai Daoda , Huang Guizao
Published: October 2021

The lift, drag and torsional moment coefficients, versus wind attack angle of iced quad bundle conductors in the cases of different conductor structure, ice and wind parameters are numerically simulated and investigated. With the Latin hypercube sampling and numerical simulation, sampling points are designed and datasets are created. Set the number of sub-conductors, wind attack angle, bundle spacing, ice accretion angle, ice thickness, wind velocity and diameter of the conductor as the input variables, a prediction model for the lift, drag and moment coefficients of iced quad bundle conductors is created, trained and tested based on the dataset and extra-trees algorithm. The final integrated prediction model is further validated by applying the aerodynamic coefficients from the prediction model and numerical simulation, respectively, to analyse the galloping features. The developed efficient prediction model for the aerodynamic coefficients of iced quad bundle conductors plays an important role in the quick investigation, prediction and early warning of galloping.
Relationship between early language competence and cognitive emotion regulation in adolescence
Authors: Griffiths Sarah , Suksasilp Chatrin , Lucas Laura , Sebastian Catherine L. , Norbury Courtenay ,   the SCALES team
Published: October 2021

Cognitive emotion regulation improves throughout adolescence and promotes good mental health. Here, we test whether language skills at school entry predict success in emotion regulation in an experimental task at age 10–11, using longitudinal data from the Surrey Communication and Language in Education Study. We additionally compared the performance of children with and without language disorder (LD). Across the whole sample (
N
= 344), language skills at school entry predicted emotion regulation success in Year 6 (
β
= 0.23), over and above the concurrent association between language and regulation success. There was no evidence that children with LD that could engage in the task were less successful regulators compared to peers with typical language. However, a quarter of children with LD were unable to complete the task. These children had more severe language difficulties, lower non-verbal IQ and more comorbid conditions. This has implications for clinicians addressing mental health needs for children with neurodevelopmental conditions that affect language, as conversations about emotions and emotion regulation are an integral part of therapy. The longitudinal relationship between language skills and the capacity to use temporal distancing for emotion regulation in early adolescence suggests that language may drive improvements in emotion regulation.
Benefits and costs of self-paced preparation of novel task instructions
Authors: Reimer Christina B. , Chen Zhang , Verbruggen Frederick
Published: October 2021

Rapidly executing novel instructions is a critical ability. However, it remains unclear whether longer preparation of novel instructions improves performance, and if so, whether this link is modulated by performance benefits and costs of preparation. Regarding the first question, we reanalysed previous data on novel instruction implementation and ran Experiment 1. Experiment 1 consisted of multiple mini-blocks, in which participants prepared four novel stimulus–response (S-R) mappings in a self-paced instruction phase. After participants indicated they were ready, one of the four stimuli was presented and they responded. The reanalysis and Experiment 1 showed that longer preparation indeed led to better performance. To examine if preparation was modulated when the benefits of preparation were reduced, we presented the correct response with the stimulus on some trials in Experiments 2 and 3. Preparation was shorter when the probability that the correct response was presented with the stimulus increased. In Experiment 4, we manipulated the costs of preparation by changing the S-R mappings between the instruction and execution phases on some trials. This had only limited effects on preparation time. In conclusion, self-paced preparation of novel instructions comes with performance benefits and costs, and participants adjust their preparation strategy to the task context.
Mass extinctions alter extinction and origination dynamics with respect to body size
Authors: Monarrez Pedro M. , Heim Noel A. , Payne Jonathan L.
Published: October 2021

Whether mass extinctions and their associated recoveries represent an intensification of background extinction and origination dynamics versus a separate macroevolutionary regime remains a central debate in evolutionary biology. The previous focus has been on extinction, but origination dynamics may be equally or more important for long-term evolutionary outcomes. The evolution of animal body size is an ideal process to test for differences in macroevolutionary regimes, as body size is easily determined, comparable across distantly related taxa and scales with organismal traits. Here, we test for shifts in selectivity between background intervals and the ‘Big Five’ mass extinction events using capture–mark–recapture models. Our body-size data cover 10 203 fossil marine animal genera spanning 10 Linnaean classes with occurrences ranging from Early Ordovician to Late Pleistocene (485–1 Ma). Most classes exhibit differences in both origination and extinction selectivity between background intervals and mass extinctions, with the direction of selectivity varying among classes and overall exhibiting stronger selectivity during origination after mass extinction than extinction during the mass extinction. Thus, not only do mass extinction events shift the marine biosphere into a new macroevolutionary regime, the dynamics of recovery from mass extinction also appear to play an underappreciated role in shaping the biosphere in their aftermath.
The proposed promiscuity value of an HLA can vary significantly depending on the source data used
Authors: Anaya Jordan , Baras Alexander S.
Published: October 2021

Immune checkpoint blockade, a form of immunotherapy, mobilizes a patient’s own immune system against cancer cells by releasing some of the natural brakes on T cells. Although our understanding of this process is evolving, it is thought that a patient response to immunotherapy requires tumor presentation of neoantigens to T cells and patients whose tumors present a wider array of neoantigens are more likely to derive benefit from immune checkpoint blockade1–4. Manczinger et al.5 recently reported findings that would appear contrarian to this notion in that they suggested patients with HLA alleles which bind more diverse peptides (higher promiscuity) are less likely to respond to immunotherapy. To estimate HLA promiscuity they looked at the HLA-peptide binding repertoires for class I alleles contained in the IEDB6, and obtained consistent results when performing robustness checks and subsequent analyses. Here we show that the proposed HLA promiscuity values can vary significantly across source data types and individual experiments.
DNA amplification in mixed aqueous-organic media: chemical analysis of leading polymerase chain reaction compositions
Authors: Neffati Jalel , Petrounia Ioanna , Moreira Rudy D. , Chakrabarti Raj
Published: October 2021

PCR amplification of GC-rich regions often leads to low yield and specificity. Addition of PCR-enhancing compounds is employed in order to overcome these obstacles. PCR-enhancing additives are low molecular polar organic compounds that are included as undisclosed co-solvents in commercial PCR buffers. In the interest of transparency and to permit further optimization by researchers of PCR compositions for challenging amplification problems, we studied eight PCR buffers by GC/MS to identify and quantify their co-solvents. Buffer specificity, both rich in water and salified substances, required a suitable sample preparation before injection into the GC/MS system. The aqueous phase of each buffer was replaced by an organic solvent to remove, by precipitation and filtration, salified substances which are detrimental to the GC/MS analysis. This approach has demonstrated the advantage of eliminating both water and salified substances without any loss of co-solvents. The sensitivity of the developed method was demonstrated as the main co-solvents were easily detected, identified and quantified. The methodology for identifying the co-solvents is mainly based on comparison of both library matching of acquired MS spectra with NIST library and experimental mass spectra obtained from authentic chemical standards. For the quantification of each co-solvent, deuterated Internal standards of similar structure to the cosolvents were used to correct the variable recovery caused by sample preparation, matrix effects, and ion source variability. The recovery ratio of the developed method was verified and found to be in the range 90-120 %. We then characterized the effects of specific organic co-solvents identified during PCR amplification -- using DNA melting, polymerase thermostability, polymerase activity and real-time PCR methods -- in order to elucidate their mechanism of action and to permit further optimization of their effects on amplification efficiency and specificity.
Individualized discovery of rare cancer drivers in global network context
Authors: Petrov Iurii , Alexeyenko Andrey
Published: October 2021

Late advances in genome sequencing expanded the space of known cancer driver genes several-fold. However, most of this surge was based on computational analysis of somatic mutation frequencies and/or their impact on the protein function. On the contrary, experimental research necessarily accounted for functional context of mutations interacting with other genes and conferring cancer phenotypes. Eventually, just such results become “hard currency” of cancer biology. The new method, NEAdriver employs knowledge accumulated thus far in the form of gene interaction networks and functionally annotated pathways in order to recover known and predict novel driver genes. The driver discovery was individualized by accounting for mutations’ co-occurrence in tumour genomes. For each somatic genome change, probabilistic estimates from two lanes of network analysis were combined into joint likelihoods of being a driver. Thus, ability to detect previously unnoticed candidate driver events emerged from combining individual genomic context with network perspective. The procedure was applied to ten largest cancer cohorts followed by evaluating error rates against previous cancer gene sets. The discovered driver combinations were shown to be informative on cancer outcome. We demonstrate that the individualized discovery revealed driver events which were individually rare, not detectable by other computational approaches, and related to cancer biology domains poorly covered by previous analyses. Considering the novel driver candidates and their constellations in individual tumor genomes opens a novel avenue for personalized cancer medicine.
Automatic antibiotic resistance prediction inKlebsiella pneumoniaebased on MALDI-TOF mass spectra
Authors: Guerrero-López Alejandro , Sevilla-Salcedo Carlos , Candela Ana , Hernández-García Marta , Cercenado Emilia , Olmos Pablo M. , Cantón Rafel , Muñoz Patricia , Gómez-Verdejo Vanessa , del Campo Rosa , Rodríguez-Sánchez Belén
Published: October 2021

Matrix-Assisted Laser Desorption Ionization Time-Of-Flight (MALDI-TOF) Mass Spectrometry (MS) is a reference method for microbial identification and it can be used to predict Antibiotic Resistance (AR) when combined with artificial intelligence methods. However, current solutions need time-costly preprocessing steps, are difficult to reproduce due to hyperparameter tuning, are hardly interpretable, and do not pay attention to epidemiological differences inherent to data coming from different centres, which can be critical.

We propose using a multi-view heterogeneous Bayesian model (KSSHIBA) for the prediction of AR using MALDI-TOF MS data together with their epidemiological differences. KSSHIBA is the first model that removes the ad-hoc preprocessing steps that work with raw MALDI-TOF data. In addition, due to its Bayesian probabilistic nature, it does not require hyperparameter tuning, provides interpretable results, and allows exploiting local epidemiological differences between data sources. To test the proposal, we used data from 402Klebsiella pneumoniaeisolates coming from two different domains and 20 different hospitals located in Spain and Portugal. KSSHIBA outperforms current state-of-the-art approaches in antibiotic susceptibility prediction, obtaining a 0.78 AUC score in Wild Type classification and a 0.90 AUC score in Extended-Spectrum Beta-Lactamases (ESBL)+Carbapenemases (CP)-producers. The proposal consistently removes the need for ad-hoc preprocessing by working with raw MALDI-TOF data, which, in turn, reduces the time needed to obtain the results of the resistance mechanism in microbiological laboratories. The proposed model implementation as well as both data domains are publicly available.
The maize gene maternal derepression of r1 (mdr1) encodes a DNA glycosylase that demethylates DNA and reduces siRNA expression in endosperm
Authors: Gent Jonathan I. , Higgins Kaitlin M. , Swentowsky Kyle W. , Fu Fang-Fang , Zeng Yibing , Kim Dong won , Dawe R. Kelly , Springer Nathan M. , Anderson Sarah N.
Published: October 2021

Demethylation of transposons can activate expression of nearby genes and cause imprinted gene expression in endosperm, and it is hypothesized to lead to expression of transposon siRNAs that reinforce silencing in the next generation through transfer either into egg or embryo. Here we describe maternal derepression of r1 (mdr1), which encodes a DNA glycosylase with homology to Arabidopsis DEMETER and which is partially responsible for demethylation of thousands of regions in endosperm. Instead of promoting siRNA expression in endosperm, MDR1 activity inhibits it. Methylation of most repetitive DNA elements in endosperm is not significantly affected by MDR1, with an exception of Helitrons. While maternally-expressed imprinted genes preferentially overlap with MDR1 demethylated regions, the majority of genes that overlap demethylated regions are not imprinted. Double mutant megagametophytes lacking both MDR1 and its close homolog DNG102 result in early seed failure, and double mutant microgametophytes fail pre-fertilization. These data establish DNA demethylation by glycosylases as essential in maize endosperm and pollen and suggest that neither transposon repression nor genomic imprinting are its main function in endosperm.
HOXB13 suppresses de novo lipogenesis through HDAC3-mediated epigenetic reprogramming
Authors: Lu Xiaodong , Fong Ka-wing , Wang Fang , Gritsina Galina , Baca Sylvan C. , Berchuck Jacob E. , Ross Jenny , Corey Eva , Chandel Navdeep , Catalona William J. , Yang Ximing , Freedman Matthew L. , Zhao Jonathan C. , Yu Jindan
Published: October 2021

HOXB13, a homeodomain transcription factor, critically regulates androgen receptor (AR) function and promotes androgen-dependent prostate cancer (PCa) growth. However, the functions of HOXB13 in an AR-independent context remain elusive. Here we report an essential role of HOXB13 in directly suppressing lipogenic transcriptional programs in both AR-positive and -negative PCa cells. The MEIS domain (aa70-150) of HOXB13 interacts with the histone deacetylase HDAC3, which is disrupted by HOXB13 G84E mutation that has been associated with early-onset PCa. Thus, HOXB13 wildtype (WT), but not G84E mutant, recruits HDAC3 to lipogenic enhancers to catalyze histone de-acetylation and suppress lipogenic programs. HOXB13 knockdown unleashes the expression of key lipogenic regulators such as fatty acid synthase (FASN), requiring HDAC3. Analysis of human tissues revealed that HOXB13 is lost in about 30% of metastatic castration-resistant PCa, at least in part, through DNA hypermethylation. Functionally, loss of HOXB13 leads to massive lipid accumulation in PCa cells, thereby promoting cell motility in vitro and fueling xenograft tumor metastasis in vivo, which is mitigated by pharmaceutical inhibitors of FASN. In summary, our study discovers an essential AR-independent function of HOXB13 in repressing de novo lipogenesis and inhibiting tumor metastasis and defines a subclass of PCa that may benefit from lipogenic pathway inhibitors.
Video-evoked fMRI BOLD responses are highly consistent across different data acquisition sites
Authors: Byrge Lisa , Kliemann Dorit , He Ye , Cheng Hu , Tyszka J. Michael , Adolphs Ralph , Kennedy Daniel P.
Published: October 2021

Naturalistic imaging paradigms, in which participants view complex videos in the scanner, are increasingly used in human cognitive neuroscience. Videos evoke temporally synchronized brain responses that are similar across subjects as well as within subjects, but the reproducibility of these brain responses across different data acquisition sites has not yet been quantified. Here we characterize the consistency of brain responses across independent samples of participants viewing the same videos in fMRI scanners at different sites (Indiana University and Caltech). We compared brain responses collected at these different sites for two carefully matched datasets with identical scanner models, acquisition, and preprocessing details, along with a third unmatched dataset in which these details varied. Our overall conclusion is that for matched and unmatched datasets alike, video-evoked brain responses have high consistency across these different sites, both when compared across groups and across pairs of individuals. As one might expect, differences between sites were larger for unmatched datasets than matched datasets. Residual differences between datasets could in part reflect participant-level variability rather than scanner- or data-related effects. Altogether our results indicate promise for the development and, critically, generalization of video fMRI studies of individual differences in healthy and clinical populations alike.
Chromatin changes in PIF-regulated genes parallel their rapid transcriptional response to light
Authors: González-Grandío Eduardo , Álamos Simón , Zhang Yu , Dalton-Roesler Jutta , Niyogi Krishna K. , García Hernán G. , Quail Peter H.
Published: October 2021

As sessile organisms, plants must adapt to a changing environment, sensing variations in resource availability and modifying their development in response. Light is one of the most important resources for plants, and its perception by sensory photoreceptors (e.g. phytochromes) and subsequent transduction into long-term transcriptional reprogramming have been well characterized. Chromatin changes have been shown to be involved in photomorphogenesis. However, the initial short-term transcriptional changes produced by light and what factors enable these rapid changes are not well studied. Here, we identify rapidly light-responsive, PIF (Phytochrome Interacting Factor) direct-target genes (LRP-DTGs). We found that a majority of these genes also show rapid changes in Histone 3 Lysine-9 acetylation (H3K9ac) in response to the light signal. Detailed time-course analysis of transcriptional and chromatin changes showed that, for light-repressed genes, H3K9 deacetylation parallels light-triggered transcriptional repression, while for light-induced genes, H3K9 acetylation appeared to somewhat precede light-activated transcription. However, real-time imaging of transcription elongation revealed that, in fact, H3K9 acetylation also parallels transcriptional induction. Collectively, the data raise the possibility that light-induced transcriptional and chromatin-remodeling processes are mechanistically intertwined. Histone modifying proteins involved in long term light responses do not seem to have a role in this fast response, indicating that different factors might act at different stages of the light response. This work not only advances our understanding of plant responses to light, but also unveils a system in which rapid chromatin changes in reaction to an external signal can be studied under natural conditions.
Regressive evolution of an effector following a host jump in the Irish Potato Famine Pathogen Lineage
Authors: Zess Erin K. , Dagdas Yasin F. , Peers Esme , Maqbool Abbas , Banfield Mark J. , Bozkurt Tolga O. , Kamoun Sophien
Published: October 2021

In order to infect a new host species, the pathogen must evolve to enhance infection and transmission in the novel environment. Although we often think of evolution as a process of accumulation, it is also a process of loss. Here, we document an example of regressive evolution in the Irish potato famine pathogen (Phytophthora infestans) lineage, providing evidence that a key sequence motif in the effector PexRD54 has degenerated following a host jump. We began by looking at PexRD54 and PexRD54-like sequences from acrossPhytophthoraspecies. We found that PexRD54 emerged in the common ancestor ofPhytophthoraclade 1b and 1c species, and further sequence analysis showed that a key functional motif, the C-terminal ATG8-interacting motif (AIM), was also acquired at this point in the lineage. A closer analysis showed that theP. mirabilisPexRD54 (PmPexRD54) AIM appeared unusual, the otherwise-conserved central residue mutated from a glutamate to a lysine. We aimed to determine whether this PmPexRD54 AIM polymorphism represented an adaptation to theMirabilis jalapahost environment. We began by characterizing theM. jalapaATG8 family, finding that they have a unique evolutionary history compared to previously characterized ATG8s. Then, using co-immunoprecipitation and isothermal titration calorimetry assays, we showed that both full-length PmPexRD54 and the PmPexRD54 AIM peptide bind very weakly to theM. jalapaATG8s. Through a combination of binding assays and structural modelling, we showed that the identity of the residue at the position of the PmPexRD54 AIM polymorphism can underpin high-affinity binding to plant ATG8s. Finally, we conclude that the functionality of the PexRD54 AIM was lost in theP. mirabilislineage, perhaps owing to as-yet-unknown pressure on this effector in the new host environment.

Author Summary

Pathogens evolve in concert with their hosts. When a pathogen begins to infect a new host species, known as a “host jump,” the pathogen must evolve to enhance infection and transmission. These evolutionary processes can involve both the gain and loss of genes, as well as dynamic changes in protein function. Here, we describe an example of a pathogen protein that lost a key functional domain following a host jump, a salient example of “regressive evolution.” Specifically, we show that an effector protein from the plant pathogenPhytopthora mirabilis, a host-specific lineage closely related to the Irish potato famine pathogenPhytopthora infestans, has a derived amino acid polymorphism that results in a loss of interaction with certain host machinery.
An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus
Authors: Navickas Albertas , Asgharian Hosseinali , Winkler Juliane , Fish Lisa , Garcia Kristle , Markett Daniel , Dodel Martin , Culbertson Bruce , Miglani Sohit , Joshi Tanvi , Nguyen Phi , Zhang Steven , Stevers Nicholas , Hwang Hun-Way , Mardakheh Faraz , Goga Andrei , Goodarzi Hani
Published: October 2021

Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed novel regression-based methods to analyze ribosome profiling and alternative polyadenylation data, and identified HNRNPC as a translational controller of a specific mRNA regulon. Mechanistically, HNRNPC, in concert with PABPC4, binds near to poly(A) signals, thereby governing the alternative polyadenylation of a set of mRNAs. We found that HNRNPC and PABPC4 are downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3’ UTR lengthening and subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. We also found that a small molecule, previously shown to induce a distal-to-proximal poly(A) site switching, counteracts the HNRNPC-PABPC4 driven deregulation of alternative polyadenylation and decreases the metastatic lung colonization by breast cancer cells in vivo.
Nuclear genome of a pedinophyte pinpoints genomic innovation and streamlining in the green algae
Authors: Repetti Sonja I , Iha Cintia , Uthanumallian Kavitha , Jackson Christopher J , Chen Yibi , Chan Cheong Xin , Verbruggen Heroen
Published: October 2021

The genomic diversity underpinning high ecological and species diversity in the green algae (Chlorophyta) remains little known. Here, we aimed to track genome evolution in the Chlorophyta, focusing on loss and gain of homologous genes, and lineage-specific innovations of the Core Chlorophyta. We generated a high-quality nuclear genome for pedinophyte YPF701, a sister lineage to others in the Core Chlorophyta, and incorporated this genome in a comparative analysis with 25 other genomes from diverse Viridiplantae taxa. The nuclear genome of pedinophyte YPF701 has an intermediate size and gene number between those of most early-diverging prasinophytes and the remainder of the Core Chlorophyta. Our results suggest positive selection for genome streamlining in Pedinophyceae, independent from genome minimisation observed among prasinophyte lineages. Genome expansion was predicted along the branch leading to the UTC clade (classes Ulvophyceae, Trebouxiophyceae and Chlorophyceae) after divergence from their common ancestor with pedinophytes, with genomic novelty implicated in a range of basic biological functions. These results emphasise multiple independent signals of genome minimisation within the Chlorophyta, as well as the genomic novelty arising prior to diversification in the UTC clade, which may underpin the success of this species-rich clade in a diversity of habitats.
Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients
Authors: LaSalle Thomas J. , Gonye Anna L. K. , Freeman Samuel S. , Kaplonek Paulina , Gushterova Irena , Kays Kyle R. , Manakongtreecheep Kasidet , Tantivit Jessica , Rojas-Lopez Maricarmen , Russo Brian C. , Sharma Nihaarika , Thomas Molly F. , Lavin-Parsons Kendall M. , Lilly Brendan M. , Mckaig Brenna N. , Charland Nicole C. , Khanna Hargun K. , Lodenstein Carl L. , Margolin Justin D. , Blaum Emily M. , Lirofonis Paola B. , Sonny Abraham , Bhattacharyya Roby P. , Parry Blair Alden , Goldberg Marcia B. , Alter Galit , Filbin Michael R. , Villani Alexandra Chloe , Hacohen Nir , Sade-Feldman Moshe
Published: October 2021

Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19+ patients, 78 COVID-19− acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.
Biocide’s susceptibility and frequency of biocide resistance genes and the effect of exposure to sub-inhibitory concentrations of sodium hypochlorite on antibiotic susceptibility of Stenotrophomonas maltophilia
Authors: KazemzadehAnari Raana , Javadi Amir , Nikkhahi Farhad , Bakht Mehdi , Rostamani Mohammad , Azimi Akram , Kelishomi Fatemeh Zeynali , Alizadeh Safar Ali
Published: October 2021

The overuse of biocides in healthcare-facilities poses risk for emergence and spread of antibiotic resistance among nosocomial pathogens. Hospital-acquired infections due to S. maltophiliahave been increased. The objective of this study was to evaluate the susceptibility of S. maltophilia clinical isolates to commonly used biocides in hospitals, as well asthe frequency of biocides resistance genes among them. This study also intended to assess the effect of exposureof S. maltophilia isolates to sub-inhibitory concentrations of sodium hypochlorite upon the antimicrobial susceptibility patterns.This study included 97 S.maltophiliaisolates.Biofilm formation was determined by microtiter plate assay. The susceptibility tests of five biocides were studied against all S. maltophilia isolates by microbroth dilution method. Susceptibility of isolates to antibiotics by disk diffusion method were compared before and after exposure to sub-inhibitory concentrations of sodium hypochlorite. Presence of qacE, qacEΔ1, SugE genes was screened by PCR. Based on minimum inhibitory and bactericidal concentrations of biocidessodium hypochlorite 5% and ethyl alcohol 70% were the strongest and weakest against S. maltophilia isolates, respectively. The frequency of sugE gene resistance genes was found 90.7% in our clinical S. maltophilia isolates. None of the isolates carried qacE and qacEΔ1 gene. Exposure to sub-inhibitory concentration of sodium hypochlorite showed significantly change the susceptibility of isolates towards ceftazidime (P = .019), ticarcillin/clavulanate (P = .009), and chloramphenicol (P = .028).This study demonstrated that exposure to sub-inhibitory concentrations of sodium hypochlorite leads to reduced antibiotic susceptibility and development of multidrug-resistant S.maltophilia strains.
RNA-sequencing reveals a gene expression signature in skeletal muscle of a mouse model of age-associated post-operative functional decline
Authors: Asche-Godin Samantha L. , Graham Zachary A. , Israel Adina , Harlow Lauren M. , Huang Weihua , Wang Zhiying , Brotto Marco , Mobbs Charles , Cardozo Christopher P. , Ko Fred C.
Published: October 2021

This study aimed to characterize the effects of laparotomy on post-operative physical function and skeletal muscle gene expression in C57BL/6N mice at 3, 20 and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre- and post-operative physical functioning were assessed by forelimb grip strength and motor coordination. Laparotomy induced an age-associated post-operative decline in forelimb grip strength that was greatest in the oldest mice. In contrast, while motor coordination declined with increasing age at baseline, it was unaffected by laparotomy. Moreover, baseline physical function as stratified by motor coordination performance (low vs. high functioning) in 24-month-old mice did not differentially affect post-laparotomy reduction in grip strength. RNA sequencing of soleus muscles showed that laparotomy induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. Examples of such age-associated, metabolically important pathways that were only activated in the youngest mice after laparotomy included oxidative phosphorylation and NRF2-mediated oxidative stress response. Analysis of lipid mediators in serum and gastrocnemius muscle showed alterations in profiles of these mediators during aging and confirmed an association between such changes and functional status in gastrocnemius muscle. These findings demonstrate a mouse model of laparotomy which recapitulated some features of post-operative skeletal muscle decline in older adults following surgery, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. Future research can build upon this mouse model to study molecular mechanisms of late-life vulnerability to acute surgical stress and resiliency to counter surgery-induced physical decline.
A groupwise registration and tractography framework for cardiac myofiber architecture description by diffusion MRI: an application to the ventricular junctions
Authors: Magat Julie , Yon Maxime , Bihan-Poudec Yann , Ozenne Valéry
Published: October 2021

Background

Knowledge of the normal myocardial–myocyte orientation could theoretically allow the definition of relevant quantitative biomarkers in clinical routine to diagnose heart pathologies. A whole heart diffusion tensor template representative of the global myofiber organization over species is therefore crucial for comparisons across populations. In this study, we developed a groupwise registration and tractography framework to resolve the global myofiber arrangement of large mammalian sheep hearts. To demonstrate the potential application of the proposed method, a novel description of sub-regions in the intraventricular septum is presented.

Methods

Three explanted sheep (ovine) hearts (size ~12×8×6 cm3, heart weight ~ 150 g) were perfused with contrast agent and fixative and imaged in a 9.4T magnet. A group-wise registration of high-resolution anatomical and diffusion-weighted images were performed to generate anatomical and diffusion tensor templates. Diffusion tensor metrics (eigenvalues, eigenvectors, fractional anisotropy …) were computed to provide a quantitative and spatially-resolved analysis of cardiac microstructure. Then tractography was performed using deterministic and probabilistic algorithms and used for different purposes: i) Visualization of myofiber architecture, ii) Segmentation of sub-area depicting the same fiber organization, iii) Seeding and Tract Editing. Finally, dissection was performed to confirm the existence of macroscopic structures identified in the diffusion tensor template.

Results

The template creation takes advantage of high-resolution anatomical and diffusion-weighted images obtained at an isotropic resolution of 150 μm and 600 μm respectively, covering ventricles and atria and providing information on the normal myocardial architecture. The diffusion metric distributions from the template were found close to the one of the individual samples validating the registration procedure. Small new sub-regions exhibiting spatially sharp variations in fiber orientation close to the junctions of the septum and ventricles were identified. Each substructure was defined and represented using streamlines. The existence of a fiber-bundles in the posterior junction was validated by anatomical dissection. A complex structural organization of the anterior junction in comparison to the posterior junction was evidenced by the high-resolution acquisition.

Conclusions

A new framework combining cardiac template generation and tractography was applied on the whole sheep heart. The framework can be used for anatomical investigation, characterization of microstructure and visualization of myofiber orientation across samples. Finally, a novel description of the ventricular junction in large mammalian sheep hearts was proposed.
Blind deconvolution in autocorrelation inversion for multi-view light sheet microscopy
Authors: Corbetta Elena , Candeo Alessia , Bassi Andrea , Ancora Daniele
Published: October 2021

Combining the information coming from multi-view acquisitions is a problem of great interest in light-sheet microscopy. Aligning the views and increasing the resolution of their fusion can be challenging, especially if the setup is not fully calibrated. Here, we tackle these issues by proposing a new reconstruction method based on autocorrelation inversion that avoids alignment procedures. On top of this, we add a blind deconvolution step to improve the resolution of the final reconstruction. Our method permits us to achieve inherently aligned, highly resolved reconstructions while, at the same time, estimating the unknown point-spread function of the system.
Experimental demonstration of prenatal programming of mitochondrial aerobic metabolism lasting until adulthood
Authors: Stier Antoine , Monaghan Pat , Metcalfe Neil B.
Published: October 2021

It is increasingly being postulated that among-individual variation in mitochondrial function underlies variation in individual performance (e.g. growth rate) and state of health. It has been suggested (but not adequately tested) that environmental conditions experienced before birth have been suggested to programme postnatal mitochondrial function, with persistent effects potentially lasting into adulthood. We tested this hypothesis in an avian model by experimentally manipulating prenatal conditions (incubation temperature and stability), then measuring mitochondrial aerobic metabolism in blood cells from the same individuals during the middle of the growth period and at adulthood. Mitochondrial aerobic metabolism changed markedly across life stages, and part of these age-related changes were influenced by the prenatal temperature conditions. A high incubation temperature induced a consistent and long-lasting increase in mitochondrial aerobic metabolism. Postnatal mitochondrial aerobic metabolism was positively associated with oxidative damage on DNA but not telomere length. While we detected significant within-individual consistency in mitochondrial aerobic metabolism across life-stages, the prenatal temperature regime only accounted for a relatively small proportion (<20%) of the consistent among-individual differences we observed. Our results demonstrate that prenatal conditions can program consistent and long-lasting differences in mitochondrial function, which could potentially underlie among-individual variation in performance and health state.
Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research
Authors: Sander Timo , Ghanawi Joly , Wilson Emma , Muhammad Sajjad , Macleod Malcolm , Kahlert Ulf Dietrich
Published: October 2021

Background

Heterogeneity of results of exact same research experiments oppose a significant socio-economic burden. In vitro research presents the early step of basic science and drug development projects. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity, however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Glioblastoma is a form of brain cancer with largely unmet clinical need.

Methods

Here we use systematic review to describe reporting practices in in vitro glioblastoma research using the U87-MG cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings.

Results

In 137 identified articles, the overall methodological reporting is disappointing, e.g., the control type, mediums glucose level and cell density are reported in only 36.5, 21.2 and 16.8 percent of the articles, respectively. After adjustments for different drug concentrations and treatment durations, a three-level meta-analysis proves meaningful results heterogeneity across the studies (I2 = 70.1%).

Conclusions

Our results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, we hope that this work will raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application, not only in neuro-oncology.

Funding

We received no specific funding for this project.
SFI1 and centrin form a distal end complex critical for proper centriole architecture and ciliogenesis
Authors: Bouhlel Imène B. , Laporte Marine. H. , Bertiaux Eloïse , Giroud Alexia , Borgers Susanne , Azimzadeh Juliette , Bornens Michel , Guichard Paul , Paoletti Anne , Hamel Virginie
Published: October 2021

Over the course of evolution, the function of the centrosome has been conserved in most eukaryotes, but its core architecture has evolved differently in some clades, as illustrated by the presence of centrioles in humans and a spindle pole body in yeast (SPB). Consistently, the composition of these two core elements has diverged greatly, with the exception of centrin, a protein known to form a complex with Sfi1 in yeast to structurally initiate SPB duplication. Even though SFI1 has been localized to human centrosomes, whether this complex exists at centrioles and whether its function has been conserved is still unclear. Here, using conventional fluorescence and super-resolution microscopies, we demonstrate that human SFI1 is a bona fide centriolar protein localizing to the very distal end of the centriole, where it associates with a pool of distal centrin. We also found that both proteins are recruited early during procentriole assembly and that depletion of SFI1 results in the specific loss of the distal pool of centrin, without altering centriole duplication in human cells, in contrast to its function for SPB. Instead, we found that SFI1/centrin complexes are essential for correct centriolar architecture as well as for ciliogenesis. We propose that SFI1/centrin complexes may guide centriole growth to ensure centriole integrity and function as a basal body.
Diversity of SARS-CoV-2 genome among various strains identified in Lucknow, Uttar Pradesh
Authors: Sahoo Biswajit , Maurya Pramod Kumar , Tripathi Ratnesh Kumar , Agarwal Jyotsana , Tiwari Swasti
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a significant challenge worldwide. Rapid genome sequencing of SARS-CoV-2 is going on across the globe to detect mutations and genomic modifications in SARS-CoV-2. In this study, we have sequenced twenty-three SARS-CoV-2 positive samples collected during the first pandemic from the state of Uttar Pradesh, India. We observed a range of already reported mutations (2-22), including; D614G, L452R, Q613H, Q677H, T1027I in the S gene; S194L in the N gene; Q57H, L106F, T175I in the ORF3. Few unreported mutations such as P309S in the ORF1ab gene; T379I in the N gene; and L52F, V77I in the ORF3a gene were also detected. Phylogenetic genome analysis showed similarity with other SARS-CoV-2 viruses reported from Uttar Pradesh. The observed mutations may be associated with SARS-CoV-2 virus pathogenicity or disease severity.