bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic neural activity predisposes susceptibility to a body illusion
Authors: Hsu Tzu-Yu , Zhou Ji-Fan , Northoff Georg , Yeh Su-Ling , Lane Timothy Joseph
Published: September 2021

Susceptibility to the rubber hand illusion (RHI) varies. Thus far, however, there is no consensus as regards how to explain this variation. Previous studies, focused on the role of multisensory integration, have searched for neural correlates of the illusion. Those studies, however, have failed to identify a sufficient set of functionally specific neural correlates. An alternative explanation of the illusion is that it results from demand characteristics, chiefly variability in the disposition to respond to imaginative suggestion: the degree to which intrinsic neural activity allows for a blurring of boundaries between self and external objects. Some evidence suggests that frontal α power is one means of tracking neural instantiations of self; therefore, we hypothesized that the higher the frontal α power during eyes-closed resting state, the more stable the self. As a corollary, we infer that the more stable the self, the less susceptible are participants to a blurring of boundaries—to feeling that the rubber hand belongs to them. Indeed, we found that frontal α amplitude oscillations negatively correlate with susceptibility. Moreover, since α and δ oscillations seem to be associated in pathological states that allow for a blurring of boundaries between self and external objects, we conjectured that the high frontal α power observed in low-RHI participants is modulated by δ frequency oscillations. Indeed, we found this to be the case. Based on our findings we propose that the two explanatory frameworks might be complementary: that is, the neural correlates of multisensory integration might be necessary for the RHI, but a sufficient explanation requires investigation of variable intrinsic neural activity that acts to modulate how the brain responds to incompatible sensory stimuli.

Highlights

~Intrinsic frontal α power negatively correlates with susceptibility to the RHI.

~Intrinsic α power modulated by δ oscillations varies with susceptibility to the RHI.

~Sufficient explanation of RHI requires understanding of intrinsic neural dispositions that regulate the boundary between self and the external world.
iCOMIC: a graphical interface-driven bioinformatics pipeline for analyzing cancer omics data
Authors: Anilkumar Sithara Anjana , Maripuri Devi Priyanka , Moorthy Keerthika , Ganesh Sai Sruthi Amirtha , Philip Philge , Banerjee Shayantan , Sudhakar Malvika , Raman Karthik
Published: September 2021

Despite the tremendous increase in omics data generated by modern sequencing technologies, their analysis can be tricky and often requires substantial expertise in bioinformatics. To address this concern, we have developed a user-friendly pipeline to analyze (cancer) genomic data that takes in raw sequencing data (FASTQ format) as input and outputs insightful statistics on the nature of the data. Our iCOMIC toolkit pipeline can analyze whole-genome and transcriptome data and is embedded in the popular Snakemake workflow management system. iCOMIC is characterized by a user-friendly GUI that offers several advantages, including executing analyses with minimal steps, eliminating the need for complex command-line arguments. The toolkit features many independent core workflows for both whole genomic and transcriptomic data analysis. Even though all the necessary, well-established tools are integrated into the pipeline to enable ‘out-of-the-box’ analysis, we provide the user with the means to replace modules or alter the pipeline as needed. Notably, we have integrated algorithms developed in-house for predicting driver and passenger mutations based on mutational context and tumor suppressor genes and oncogenes from somatic mutation data. We benchmarked our tool against Genome In A Bottle (GIAB) benchmark dataset (NA12878) and got the highest F1 score of 0.971 and 0.988 for indels and SNPs, respectively, using the BWA MEM - GATK HC DNA-Seq pipeline. Similarly, we achieved a correlation coefficient of r=0.85 using the HISAT2-StringTie-ballgown and STAR-StringTie-ballgown RNA-Seq pipelines on the human monocyte dataset (SRP082682). Overall, our tool enables easy analyses of omics datasets, with minimal steps, significantly ameliorating complex data analysis pipelines.

Availability:https://github.com/RamanLab/iCOMIC
Characterizing the human methylome across the life course: findings from eight UK-based studies
Authors: Walton Esther , Marioni Riccardo , Elliott Hannah R , Cox Simon R , Deary Ian J , Hughes Alun D , Tillin Therese , Kumari Meena , Woofenden Tom , Castillo-Fernandez Juan E , Bell Jordana T , Goodman Alissa , Ploubidis George , Tilling Kate , Suderman Matthew , Gaunt Tom R , Dunn Erin C , Smith Andrew , Relton Caroline L
Published: September 2021

Variation in DNA methylation (DNAm) is associated with multiple biological processes that track growth and development, ageing and age-related diseases. However, there is little understanding of what constitutes typical patterns of DNAm variation and how these patterns change across the life course. In this study, we synthesised a map of the human methylome across the life course, focussing on changes in variability and mean DNAm.

Harmonizing DNAm datasets across eight longitudinal and cross-sectional UK-based studies, we meta-analysed n=13,215 blood samples from n=7,037 unique individuals from birth to 98 years of age. Changes in CpG-specific variability and means were described across the life course using a meta-regression framework. CpG-specific associations of variability or mean DNAm in relation to the likelihood of association with 100 traits linked to environmental exposures, health and disease were tested within and across ten developmental age bins across the life course.

Age was linked to DNAm variability at 29,212 CpG sites. On average, we observed a 1.26 fold increase in DNAm variability per year across the life course. 33,730 CpGs displayed changes in mean DNAm, with 64% of these loci showing decreases in DNAm over time. CpG sites linked to traits were in general more variable across the life course.

Our study provides, for the first time, a map of the human methylome across the life course, which is publicly accessible through a searchable online database. This resource allows researchers to query CpG-specific trajectories from birth to old age and link these to health and disease.
A Genotype-to-Phenotype Modeling Framework to Predict Human Pathogenicity of Novel Coronaviruses
Authors: Davis Phillip , Russell Joseph A.
Published: September 2021

Leveraging prior viral genome sequencing data to make predictions on whether an unknown, emergent virus harbors a ‘phenotype-of-concern’ has been a long-sought goal of genomic epidemiology. A predictive phenotype model built from nucleotide-level information alone has previously been considered un-tenable with respect to RNA viruses due to the ultra-high intra-sequence variance of their genomes, even within closely related clades. Building from our prior work developing a degenerate k-mer method to accommodate this high intra-sequence variation of RNA virus genomes for modeling frameworks, and leveraging a taxonomic ‘group-shuffle-split’ paradigm on complete coronavirus assemblies from prior to October 2018, we trained multiple regularized logistic regression classifiers at the nucleotide k-mer level capable of accurately predicting withheld SARS-CoV-2 genome sequences as human pathogens and accurately predicting withheld Swine Acute Diarrhea Syndrome coronavirus (SADS-CoV) genome sequences as non-human pathogens. LASSO feature selection identified several degenerate nucleotide predictor motifs with high model coefficients for the human pathogen class that were present across widely disparate classes of coronaviruses. However, these motifs differed in which genes they were present in, what specific codons were used to encode them, and what the translated amino acid motif was. This emphasizes the importance of a phenetic view of emerging pathogenic RNA viruses, as opposed to the canonical phylogenetic interpretations most-commonly used to track and manage viral zoonoses. Applying our model to more recent Orthocoronavirinae genomes deposited since October 2018 yields a novel contextual view of pathogen-potential across bat-related, canine-related, porcine-related, and rodent-related coronaviruses and critical adaptations which may have contributed to the emergence of the pandemic SARS-CoV-2 virus. Finally, we discuss the utility of these predictive models (and their associated predictor motifs) to novel biosurveillance protocols that substantially increase the ‘pound-for-pound’ information content of field-collected sequencing data and make a strong argument for the necessity of routine collection and sequencing of zoonotic viruses.
Age-related differences in performance and fatigability during an isometric quadriceps intermittent fatigue test
Authors: Varesco Giorgio , Luneau Eric , Féasson Léonard , Lapole Thomas , Rozand Vianney
Published: September 2021

The aim of the present study was to investigate age-related differences in fatigability induced by an isometric quadriceps intermittent fatiguing test in young (<35 years old), old (>60 years old) and very old (>80 years old) men and women. Maximal force loss, contractile function and voluntary activation of the knee extensors were evaluated throughout an isometric fatiguing test using femoral nerve magnetic stimulations. Older adults performed more contractions (index of relative performance) than young (P = 0.046) and very old adults (P = 0.007), without differences between young and very old adults. Total work (absolute performance) was greater for young and old adults compared to very old adults (P < 0.001), without differences between young and old adults. At exhaustion, force loss was greater for young (−28 ± 9%) compared to old adults (−19 ± 8%), but not very old adults (−23 ± 8%). The response to femoral nerve stimulation decreased similarly at exhaustion for the three age groups, indicating similar alteration in contractile function with age. No impairment in voluntary activation was observed. Impairments in neuromuscular parameters were similar for men and women. This study showed that older adults were less fatigable than young adults during an isometric intermittent fatiguing task of the knee extensors. This greater fatigue resistance was not maintained in very old adults independent of sex. Fatigability at exhaustion was likely due to impairments in contractile function for the three age groups.
Quantification of new and archived Diaphorina citri transcriptome data using a chromosomal length D. citri genome assembly reveals the vector’s tissue-specific transcriptional response to citrus greening disease
Authors: Mann Marina , Saha Surya , Cicero Joseph M. , Pitino Marco , Moulton Kathy , Cano Lilianna , Hunter Wayne B. , Mueller Lukas A. , Heck Michelle
Published: September 2021

Background

Huanglongbing (HLB) is the most serious disease of citrus. HLB is caused by the obligate, intracellular bacterium “Candidatus Liberibacter asiaticus” (CLas). CLas is transmitted by Diaphorina citri, the Asian citrus psyllid. Development of transmission blocking strategies to manage HLB relies on knowledge of CLas-D. citri interactions at the molecular level. Prior transcriptome analyses of CLas-infected and un-infected D. citri point to changes in psyllid biology due to CLas-infection. These studies relied on incomplete versions of the D. citri genome, lacked proper host plant controls, and/or were analyzed using different statistical approaches. Therefore, we used standardized experimental and computational approaches to identify differentially expressed genes in both CLas (+) and CLas (-) D. citri. The comparative analysis utilized the newest chromosomal length D. citri genome assembly Diaci_v3. In this work, we present a quantitative transcriptome analysis of excised heads, salivary glands, midguts and bacteriomes from CLas (+) and CLas (-) insects.

Results

Each organ had unique transcriptome profiles and responses to CLas infection. Though most psyllids were infected with CLas, CLas-derived transcripts were not detected in all organs. By analyzing the midgut dataset using both the Diaci_v1.1 and v3.0 D. citri genomes, we showed that improved genome assembly led to significant and quantifiable differences in RNAseq data interpretation.

Conclusions

Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.
The Siberian wild apple, Malus baccata (L.) Borkh., is an additional contributor to the genomes of cultivated European and Chinese apples
Authors: Chen Xilong , Cornille Amandine , An Na , Xing Libo , Ma Juanjuan , Zhao Caiping , Wang Yibin , Han Mingyu , Zhang Dong
Published: September 2021

It is crucial to understand domestication to unravel the evolutionary processes that shape the divergence of populations. Differences in life-history traits have probably led to marked differences in the mode and speed of evolution between trees and annuals, particularly the extent of crop-wild gene flow during domestication. Apple is an iconic tree and major fruit crop grown worldwide. The contribution of wild apple species to the genetic makeup of the cultivated apple genome remains a topic of intense investigations. We used population genomics in combination with SNPs to investigate the contributions of the two known wild apple relatives, Malus sylvestris and Malus sieversii, and a supposed contributor, Malus baccata, to European and Chinese rootstock and dessert genomes, with a focus on the extent of wild-crop gene flow during apple domestication. We showed that the European dessert and rootstock apples form a specific gene pool, whereas the Chinese dessert and rootstock apples were a mixture of three wild gene pools. Coalescent-based inferences and gene flow estimates indicated that M. baccata is an additional contributor to the genome of both European and Chinese cultivated apples through wild-to-crop introgressions. We also confirmed previous results on the contribution of M. sylvestris to the cultivated apple genome, and provided insights into the origin of the apple rootstock. This study further demonstrates the role of gene flow during apple domestication, as seen in other woody perennials, and show that domestication of the apple tree involved several wild apple species.
Connectome Spatial Smoothing (CSS): concepts, methods, and evaluation
Authors: Mansour L. Sina , Seguin Caio , Smith Robert E. , Zalesky Andrew
Published: September 2021

Structural connectomes are increasingly mapped at high spatial resolutions comprising many hundreds—if not thousands—of network nodes. However, high-resolution connectomes are particularly susceptible to image registration misalignment, tractography artifacts, and noise, all of which can lead to reductions in connectome accuracy and test-retest reliability. We investigate a network analogue of image smoothing to address these key challenges. Connectome Spatial Smoothing (CSS) involves jointly applying a carefully chosen smoothing kernel to the two endpoints of each tractography streamline, yielding a spatially smoothed connectivity matrix. We develop computationally efficient methods to perform CSS using a matrix congruence transformation and evaluate a range of different smoothing kernel choices on CSS performance. We find that smoothing substantially improves the identifiability, sensitivity, and test-retest reliability of high-resolution connectivity maps, though at a cost of increasing storage burden. For atlas-based connectomes (i.e. low-resolution connectivity maps), we show that CSS marginally improves the statistical power to detect associations between connectivity and cognitive performance, particularly for connectomes mapped using probabilistic tractography. CSS was also found to enable more reliable statistical inference compared to connectomes without any smoothing. We provide recommendations on optimal smoothing kernel parameters for connectomes mapped using both deterministic and probabilistic tractography. We conclude that spatial smoothing is particularly important for the reliability of high-resolution connectomes, but can also provide benefits at lower parcellation resolutions. We hope that our work enables computationally efficient integration of spatial smoothing into established structural connectome mapping pipelines.

Highlights

We establish a network equivalent of image smoothing for structural connectomes.

Connectome Spatial Smoothing (CSS) improves connectome test-retest reliability, identifiability and sensitivity.

CSS also facilitates reliable inference and improves power to detect statistical associations.

Both high-resolution and atlas-based connectomes can benefit from CSS.
A single-cell reference atlas delineates CD4+T cell subtype-specific adaptation during acute and chronic viral infections
Authors: Andreatta Massimo , Sherman Zachary , Tjitropranoto Ariel , Kelly Michael C. , Ciucci Thomas , Carmona Santiago J.
Published: September 2021

CD4+T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. The multifaceted roles of CD4+T cells, including their help to innate cells, CD8+T and B cells and their support for long-lived immunity rely on a profound functional heterogeneity. While multiple CD4+T cell subtypes and their key transcriptional regulators have been identified, there is a lack of consistent definition for CD4+T cell transcriptional states. In addition, the progressive changes affecting CD4+T cell subtypes during and after immune responses remain poorly defined. Taking advantage of single-cell transcriptomics, efficient computational methods, and robust animal models, we characterize the transcriptional landscape of CD4+T cells responding to self-resolving and chronic viral infections. We build a comprehensive atlas of virus-specific CD4+T cells and their evolution over time, and identify six major distinct cell states that are consistently observed in acute and chronic infections. During the course of acute infection, T cell composition progressively changes from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, T cells in persistent infections fail to transition from effector to memory states, and acquire distinct, chronicity-associated transcriptional programs. By single-cell T cell receptor (TCR) sequencing analysis, we characterize the clonal structure of virus-specific CD4+T cells across individuals and T cell subtypes. We find that virus-specific CD4+T cell responses are mainly private across individuals and that most T cells differentiate into all subtypes independently of their TCR, in both acute and chronic infections. Finally, we show that our CD4+T cell atlas can be used as a reference to accurately interpret cell states in external single-cell datasets. Overall, this study describes a previously unappreciated level of adaptation of the transcriptional states of CD4+T cells responding to viruses and provides a new computational resource for CD4+T cell analysis, available online athttps://spica.unil.ch.
Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk
Authors: Kwon Jaedeok , Suessmilch Maria , McColl Alison , Cavanagh Jonathan , Morris Brian J.
Published: September 2021

Exposure to infection in utero predisposes towards psychiatric diseases such as autism, depression and schizophrenia in later life. The mechanisms involved are typically studied by administering mimetics of double-stranded (ds) RNA viral or bacterial infection to pregnant rats or mice. The effect of single-stranded (ss) virus mimetics has been largely ignored, despite evidence linking prenatal ss virus exposure specifically with psychiatric disease. Understanding the effects of gestational ss virus exposure has become even more important with the current SARS-CoV-2 pandemic. In this study, in pregnant mice, we compare directly the effects, on the maternal blood, placenta and the embryonic brain, of maternal administration of ds-virus mimetic poly I:C (to activate toll-like receptor 3, TLR3) and ss-virus mimetic resiquimod (to activate TLR7/8). We find that, 4h after the administration, both poly I:C and resiquimod elevated the levels of IL-6, TNFα, and chemokines including CCL2 and CCL5, in maternal plasma. Both agents also increased placental mRNA levels of IL-6 and IL-10, but only resiquimod increased placental TNFα mRNA. In foetal brain, poly I:C produced no detectable immune-response-related increases, whereas pronounced increases in cytokine (e.g. Il-6, Tnfα) and chemokine (e.g. Ccl2, Ccl5) expression were observed with maternal resiquimod administration. The data show substantial differences between the effect of maternal exposure to a TLR7/8 activator as compared to a TLR3 activator. There are significant implications for future modelling of diseases where maternal ss virus exposure contributes to environmental disease risk in offspring.
A conformational switch controlling the toxicity of the prion protein
Authors: Frontzek Karl , Bardelli Marco , Senatore Assunta , Henzi Anna , Reimann Regina R. , Bedir Seden , Marino Marika , Hussain Rohanah , Jurt Simon , Meisl Georg , Pedotti Mattia , Mazzola Federica , Siligardi Giuliano , Zerbe Oliver , Losa Marco , Knowles Tuomas , Lakkaraju Asvin , Zhu Caihong , Schwarz Petra , Hornemann Simone , Holt Matthew G. , Simonelli Luca , Varani Luca , Aguzzi Adriano
Published: September 2021

Prion infections cause conformational changes of PrPC and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (“H-latch”) altering the flexibility of the α2-α3 and β2-α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unable to form the H-latch conferred resistance to prion infection. High-affinity ligands that prevented H-latch induction repressed prion-related neurodegeneration in organotypic cerebellar cultures. We then selected phage-displayed ligands binding wild-type PrPC, but not PrP2Cys. These binders depopulated H-latched conformers and conferred protection against prion toxicity. Finally, brain-specific expression of an antibody rationally designed to prevent H-latch formation, prolonged the life of prion-infected mice despite unhampered prion propagation, confirming that the H-latch is causally linked to prion neurotoxicity.
Endogenous virus sRNA regulates gene expression following genome shock in tomato hybrids
Authors: Lopez-Gomollon Sara , Müller Sebastian Y. , Baulcombe David C.
Published: September 2021

Hybridization and environmental stress trigger genome shock that perturbs patterns of gene expression leading to phenotypic changes. In extreme examples it is associated to transposon mobilization and genome rearrangement. Here we discover a novel alternative mechanism in interspecific Solanum hybrids in which changes to gene expression were associated with DCL2-mediated small (s)RNAs derived from endogenous (para)retroviruses (EPRVs). Correspondingly, the altered patterns of gene expression overlapped with the effects of dcl2 mutation and the changes to sRNA profiles involved 22nt species produced in the DCL2 biogenesis pathway. These findings implicate hybridization-induced genome shock leading to EPRV activation and sRNA silencing as causing changes in gene expression. Such hybridization-induced variation in gene expression could increase the range of traits available for selection in natural evolution or in breeding for agriculture.
Molecular insights into RNA recognition and gene regulation by the TRIM-NHL protein Mei-P26
Authors: Salerno-Kochan Anna , Horn Andreas , Ghosh Pritha , Nithin Chandran , Kościelniak Anna , Strauss Daniela , Rossbach Oliver , Bujnicki Janusz M. , Gaik Monika , Medenbach Jan , Glatt Sebastian
Published: September 2021

The TRIM-NHL protein Meiotic P26 (Mei-P26) acts as a regulator of cell fate in Drosophila. Its activity is critical for ovarian germline stem cell maintenance, differentiation of oocytes and spermatogenesis. Mei-P26 functions as a post-transcriptional regulator of gene expression, however, the molecular details of how its NHL domain selectively recognizes and regulates its mRNA targets have remained elusive. Here, we present the crystal structure of the Mei-P26 NHL domain at 1.6 Å resolution and identify key amino acids that confer substrate specificity and distinguish Mei-P26 from closely related TRIM-NHL proteins. Furthermore, we identify mRNA targets of Mei-P26 in cultured Drosophila cells and show that Mei-P26 can act as either a repressor or activator of gene expression on different RNA targets. Our work reveals the molecular basis of RNA recognition by Mei-P26 and the fundamental functional differences between otherwise very similar TRIM-NHL proteins.
STAT3-mediated allelic imbalance of novel genetic variant rs1047643 and B cell specific super-enhancer in association with systemic lupus erythematosus
Authors: Zhang Yanfeng , Day Kenneth , Absher Devin M.
Published: September 2021

Mapping of allelic imbalance (AI) at heterozygous loci has the potential to establish links between genetic risk for disease and biological function. Leveraging multi-omics data for AI analysis and functional annotation, we discovered a novel functional risk variant rs1047643 at 8p23 in association with SLE. This variant displays dynamic AI of chromatin accessibility and allelic expression on FDFT1 gene in B cells with SLE. We further found a B-cell restricted super-enhancer (SE) that physically contacts with this SNP-residing locus, an interaction that also appears specifically in B cells. Quantitative analysis of open chromatin and DNA methylation profiles further demonstrated that the SE exhibits aberrant activity in B cell development with SLE. Functional studies identified that STAT3, a master factor associated with autoimmune diseases, directly regulates both the AI of risk variant and the activity of SE in cultured B cells. Our study reveals that STAT3-mediated SE activity and cis-regulatory effects of SNP rs1047643 at 8p23 locus are associated with B cell deregulation in SLE.
A contribution to the larval amphibian microbiome: characterization of bacterial microbiome of Ichthyophis bannanicus (Order: Gymnophiona) and comparison with the other two amphibian orders
Authors: Rajput Amrapali Prithvisingh , Zhou Shipeng , Meegaskumbura Madhava
Published: September 2021

It is known that animal-associated microbiomes form indispensable relationships with hosts and are responsible for many functions important for host-survival. Next-gen driven approaches documenting the remarkable diversity of microbiomes have burgeoned, with amphibians too, benefiting from such treatments. The microbiome of Gymnophiona (caecilians), one of the three amphibian orders, constituting of 3% of amphibians, however, remains almost unknown. The present study aims to address this knowledge gap through analysis of the microbiome of Ichthyophis bannanicus. As these caecilian larvae are aquatic and hence exposed to a greater propensity for bacterial microbiomic interchange, we hypothesize that bacterial phyla would overlap between gut and skin. Further, from the host-specificity patterns observed in other vertebrate taxa, we hypothesize that Gymnophiona have different dominant gut bacterial microbiomes at a higher taxonomic level when compared to the larvae of the other two amphibian orders (Anura and Caudata). We used 16S rRNA gene amplicon sequencing based on Illumina Nova sequencing platform to characterize and compare the gut (represented by faecal samples) and skin microbiome of I. bannanicus larvae (N = 13), a species distributed across South-East-Asia and the only caecilian species occurring in China. We compared our gut microbiome results with published anuran and caudate larval microbiomes. For I. bannanicus, a total of 4,053 operational taxonomic units (OTU) across 13 samples were detected. Alpha-diversity indices were significant between gut and skin samples. Non-metric multidimensional scaling analysis suggest that gut and skin samples each contained a distinct microbiome at OTU level. We record significant differences between the bacterial phyla of gut and skin samples in larvae of I. bannanicus. The study provides an overview of gut and skin bacterial microbiomes of a caecilian, while highlighting the major differences between larval microbiomes of the three amphibian orders. We find a partial overlap of gut bacterial microbiomes at phylum level for the three orders; however, the relative abundance of the dominant phyla is distinct. The skin and gut microbiomes are distinct with little overlap of species, highlighting that gut-skin axis is weak. This in turn suggests that many of the microbial species on skin and gut are functionally specialized to those locations. We also show that the skin microbiome is more diverse than the gut microbiome at species level; however, a reason for this could be a portion of the gut microbiome not being represented in faecal samples. These first microbiome information from a caecilian lay the foundation for comparative studies of the three amphibian orders.
The E34 Phage Tailspike Protein: An in vitro characterization, Structure Prediction, Potential Interaction with S. newington LPS and Cytotoxicity Assessment to Animal Cell Line
Authors: Ayariga Joseph A. , Gildea Logan , Wu Honghzuan , Villafane Robert
Published: September 2021

The E34 phage is a member of the podoviridae family of phages, (short non-contractile tailed bacteriophages) that uses Salmonella newington as its host. This phage initiates the infection of its host via a specific interaction between its tailspike protein (TSP) and the lipopolysaccharides (LPS) of the bacterial. The E34 TSP is structurally similar and functionally equivalent to the P22 phage whose TSP has been well characterized and electron micrographs of both phages appear indistinguishable. The crystal structure of P22 phage TSP in complex with the O-antigen of S. typhimurium has been determined; and the active site of the TSP demonstrated to be the residues Asp392, Asp395 and Glu359 of the receptor binding domain. In another phage called E15, a phylogenetic relative of E34 phage, a short polysaccharide consisting of α repeating units is responsible for the interaction between the E15 phage and Salmonella anatum’s LPS leading to the adsorption of the phage to the bacteria. Studies on E34 phage shows that it interacts with Salmonella newington’s O antigen polysaccharide component of the LPS, this polysaccharide consists of mannosyl-rhamnosyl-galactose repeating units joined together by β-galactosyl linkages. However, no data exist regarding the specific residues of E34 TSP that are responsible for LPS binding and hydrolysis. In this study, the tailspike gene was cloned onto vector pET30a-LIC and expressed as a fusion protein termed the extended E34 TSP (EE34 TSP). We characterized the protein based on resistance to heat, SDS, and proteases; showing that the protein is heat resistant, shows aberrant electrophoretic mobility in the presence of SDS gradient, and actively binds to P22 phage heads to form hybrid phages that cannot infect P22 host. We also demonstrate via in silico study that the E34 TSP binds to and hydrolyses the O-antigen of its host via the ALA250, SER279 and ASP280 residues. Finally, testing E34 phage ability to protect Vero cells from Salmonella infection shows highly encouraging results, implying that E34 phage can be used in therapeutic/preventive medicine.
New Insights into the Mechanisms Used by Inhibitors Targeting Glutamine Metabolism in Cancer Cells
Authors: Milano Shawn K. , Huang Qingqiu , Nguyen Thuy-Tien T. , Ramachandran Sekar , Finke Aaron , Kriksunov Irina , Schuller David , Szebenyi Marian , Arenholz Elke , McDermott Lee A. , Sukumar N. , Cerione Richard A. , Katt William P.
Published: September 2021

Many cancer cells become dependent on glutamine metabolism to compensate for glycolysis being uncoupled from the TCA cycle. The mitochondrial enzyme Glutaminase C (GAC) satisfies this ‘glutamine addiction’ by catalyzing the first step in glutamine metabolism, making it an attractive drug target. Despite one of the allosteric inhibitors (CB-839) being in clinical trials, none of the drugs targeting GAC are approved for cancer treatment and their mechanism of action is not well understood. A major challenge has been the rational design of better drug candidates: standard cryo-cooled X-ray crystal structures of GAC bound to CB-839 and its analogs fail to explain their potency differences. Here, we address this problem by using an emerging technique, serial room temperature crystallography, which enabled us to observe clear differences between the binding conformations of inhibitors with significantly different potencies. A computational model was developed to further elucidate the molecular basis of inhibitor potency. We then corroborated the results from our modeling efforts by using recently established fluorescence assays that directly read-out inhibitor binding to GAC. Together, these findings provide new insights into the mechanisms used by a major class of allosteric GAC inhibitors and for the future rational design of more potent drug candidates.
Oxidized thioredoxin-1 restrains the NLRP1 inflammasome
Authors: Ball Daniel P. , Wang Alvin E. , Warren Charles D. , Wang Qinghui , Griswold Andrew R. , Rao Sahana D. , Bachovchin Daniel A.
Published: September 2021

At least six human proteins detect danger-associated signals, assemble into complexes called inflammasomes, and trigger pyroptotic cell death. NLRP1 was the first protein discovered to form an inflammasome, but the danger signals and molecular mechanisms that control its activation have not yet been fully established. Here, we report that the NACHT-LRR region of NLRP1 directly binds to oxidized form of thioredoxin-1 (TRX1). We found that NLRP1 requires the ATPase activity of its NACHT domain to associate with TRX1, and that this interaction represses inflammasome activation. Moreover, we discovered that several patient-derived missense mutations in the NACHT-LRR region of NLRP1 weaken TRX1 binding, leading to inflammasome hyperactivation and autoinflammatory disease. Overall, our results establish that oxidized TRX1 binds to and restrains the NLRP1 inflammasome, thereby revealing a link between the cellular redox environment and innate immunity.
Diversity and distribution of sediment bacteria across an ecological and trophic gradient
Authors: Sauer Hailey M. , Hamilton Trinity L. , Anderson Rika E. , Umbanhowar Charles E. , Heathcote Adam J.
Published: September 2021

Can we cluster bacterial sediment communities based on lake size, depth, and trophic status? Or, are bacterial microbial communities an emergent property of their geography, integrating regional physical and climatic conditions? Lakes in Minnesota are uniquely situated to address these questions because of their wide geographic range and variability in size and basin land-use. In this study, we selected twenty lakes with varying morphological and chemical properties across four ecological regions of Minnesota. Our objectives were to (i)) evaluate the diversity and spatial variation of the bacterial community at the sediment-water interface and (ii) determine how lake location and watershed land-use impact aqueous chemistry and influence community structure. Our data indicate that sediment communities from similar depth intervals are more likely to cluster by ecological region rather than any individual lake properties (e.g., trophic status, TP concentration, lake depth). However, composition is tied to a given lake, wherein samples from the same core were more alike than samples at similar depths across lakes. Our results illustrate the diversity within lake sediment microbial communities and provide insight into relationships between taxonomy, physicochemical, and geographic properties of north temperate lakes.
Current protein structure predictors do not produce meaningful folding pathways
Authors: Outeiral Carlos , Nissley Daniel A. , Deane Charlotte M.
Published: September 2021

Protein structure prediction has long been considered a gateway problem for understanding protein folding. Recent advances in deep learning have achieved unprecedented success at predicting a protein’s crystal structure, but whether this achievement relates to a better modelling of the folding process remains an open question. In this work, we compare the pathways generated by state-of-the-art protein structure prediction methods to experimental folding data. The methods considered were AlphaFold 2, RoseTTAFold, trRosetta, RaptorX, DMPfold, EVfold, SAINT2 and Rosetta. We find evidence that their simulated dynamics capture some information about the folding pathwhay, but their predictive ability is worse than a trivial classifier using sequence-agnostic features like chain length. The folding trajectories produced are also uncorrelated with parameters such as intermediate structures and the folding rate constant. These results suggest that recent advances in protein structure prediction do not yet provide an enhanced understanding of the principles underpinning protein folding.
N-Representable one-electron reduced density matrices reconstruction at non-zero temperatures
Authors: Launay Yoann , Gillet Jean-Michel
Published: September 2021

This article retraces different methods that have been explored to account for the atomic thermal motion in the reconstruction of one-electron reduced density matrices from experimental X-ray structure factors (XSF) and directional Compton profiles (DCP). Attention has been paid to propose the simplest possible model, which obeys the necessary N-representability conditions, while accurately reproducing all available experimental data. The deconvolution of thermal effects makes it possible to obtain an experimental static density matrix, which can directly be compared with theoretical 1-RDM (reduced density matrix). It is found that above a 1% statistical noise level, the role played by Compton scattering data becomes negligible and no accurate 1-RDM is reachable. Since no thermal 1-RDM is available as a reference, the quality of an experimentally derived temperature-dependent matrix is difficult to assess. However, the accuracy of the obtained static 1-RDM, through the performance of the refined observables, is strong evidence that the Semi-Definite Programming method is robust and well adapted to the reconstruction of an experimental dynamical 1-RDM.
Accurate H-atom parameters for the two polymorphs of L-histidine at 5, 105 and 295 K
Authors: Novelli Giulia , McMonagle Charles J. , Kleemiss Florian , Probert Michael , Puschmann Horst , Grabowsky Simon , Maynard-Casely Helen E. , McIntyre Garry J. , Parsons Simon
Published: September 2021

The crystal structure of the monoclinic polymorph of the primary amino acid L-histidine has been determined for the first time by single-crystal neutron diffraction, while that of the orthorhombic polymorph has been reinvestigated with an untwinned crystal, improving the experimental precision and accuracy. For each polymorph, neutron diffraction data were collected at 5, 105 and 295 K. Single-crystal X-ray diffraction experiments were also performed at the same temperatures. The two polymorphs, whose crystal packing is interpreted by intermolecular interaction energies calculated using the Pixel method, show differences in the energy and geometry of the hydrogen bond formed along the c direction. Taking advantage of the X-ray diffraction data collected at 5 K, the precision and accuracy of the new Hirshfeld atom refinement method implemented in NoSpherA2 were probed choosing various settings of the functionals and basis sets, together with the use of explicit clusters of molecules and enhanced rigid-body restraints for H atoms. Equivalent atomic coordinates and anisotropic displacement parameters were compared and found to agree well with those obtained from the corresponding neutron structural models.
Structure of boehmite-derived γ-alumina and its transformation mechanism revealed by electron crystallography
Authors: Luo Zhiping
Published: September 2021

γ-Alumina is a widely used material, while its precise crystal structure and transformation mechanism derived from boehmite have remained unclear in the literature for decades. In this work, quantitative electron microscopy has been applied to study the crystalline structure of γ-alumina and its transformation mechanism from boehmite. Based on Rietveld refinement of electron diffraction patterns, a new tetragonal structure model, with a space group of I41/amd (No. 141), was proposed for the γ-alumina phase, with Al cations on 4a, 8c, 8d and 16g sites and O anions on the 16h site, which could provide better fits than current models. During the boehmite to γ-alumina transformation induced by e-beam irradiation, when the boehmite layers were oriented along the edge-on direction, a shrinkage caused by dehydration was directly observed. Two kinds of boehmite to γ-alumina transformation mechanisms, namely collapse and reaction mechanisms, were elucidated crystallographically in detail with new insights through an intermediate structure, and the reaction mechanism was demonstrated to produce much reduced changes in dimensions and volume, compared with the collapse mechanism. The experimental observations supported the reaction mechanism, which occurred through partial occupation of the dehydrated space by diffusion in the initial stage of the transformation, without the formation of voids that only appeared after the initial stage. Filling tetrahedral interstices of the intermediate structure with Al cations in different ways yields tetragonal or cubic γ-alumina structures, and the tetragonal structure is energetically favorable because of smaller lattice distortions required, compared with the cubic structure. The crystallographic orientation relationships of γ-alumina with the parent boehmite phase deduced from the proposed mechanisms are consistent with the experimental observations.
Preparation of polyethylene oxide single crystals via liquid gating technology and morphology design strategy
Authors: Li Shi , Zhao Jihe , Wang Xiao , Li Zhihua , Gui Xuefeng , Hu Jiwen , Lin Shudong , Tu Yuanyuan
Published: September 2021

A novel type of liquid gating technology has been developed to prepare a polyethylene oxide (PEO) single-crystal film, and the crystal growth was observed via atomic force microscopy. The self-seeding method has been widely used in the preparation of polymer single crystals, but the mechanism through which single polymer crystals are formed via the combination of liquid gating technology and the self-seeding method remains unclear. To elucidate the mechanism of this process, a series of experiments were conducted in which a dilute polymer solution was sprayed onto a mica substrate to form a single-crystal film through liquid gating technology to study the effect of the crystallization time on the morphology of a thiol PEO (mPEO-SH) crystal. Based on this research, it was found that liquid gating helps to prevent twinning during crystal growth. The combination of liquid gating and self-seeding technology thus provides a new strategy for polymer single-crystal growth.
Nanobody-aided crystallization of the transcription regulator PaaR2 from Escherichia coli O157:H7
Authors: De Bruyn Pieter , Prolič-Kalinšek Maruša , Vandervelde Alexandra , Malfait Milan , Sterckx Yann G.-J. , Sobott Frank , Hadži San , Pardon Els , Steyaert Jan , Loris Remy
Published: September 2021

paaR2–paaA2–parE2 is a three-component toxin–antitoxin module found in prophage CP-993P of Escherichia coli O157:H7. Transcription regulation of this module occurs via the 123-amino-acid regulator PaaR2, which forms a large oligomeric structure. Despite appearing to be well folded, PaaR2 withstands crystallization, as does its N-terminal DNA-binding domain. Native mass spectrometry was used to screen for nanobodies that form a unique complex and stabilize the octameric structure of PaaR2. One such nanobody, Nb33, allowed crystallization of the protein. The resulting crystals belong to space group F432, with unit-cell parameter a = 317 Å, diffract to 4.0 Å resolution and are likely to contain four PaaR2 monomers and four nanobody monomers in the asymmetric unit. Crystals of two truncates containing the N-terminal helix–turn–helix domain also interact with Nb33, and the corresponding co-crystals diffracted to 1.6 and 1.75 Å resolution.
Audiogmenter: a MATLAB toolbox for audio data augmentation
Authors: Maguolo Gianluca , Paci Michelangelo , Nanni Loris , Bonan Ludovico
Published: September 2021

Purpose

Create and share a MATLAB library that performs data augmentation algorithms for audio data. This study aims to help machine learning researchers to improve their models using the algorithms proposed by the authors.

Design/methodology/approach

The authors structured our library into methods to augment raw audio data and spectrograms. In the paper, the authors describe the structure of the library and give a brief explanation of how every function works. The authors then perform experiments to show that the library is effective.

Findings

The authors prove that the library is efficient using a competitive dataset. The authors try multiple data augmentation approaches proposed by them and show that they improve the performance.

Originality/value

A MATLAB library specifically designed for data augmentation was not available before. The authors are the first to provide an efficient and parallel implementation of a large number of algorithms.
Neuropsychological responses of consumers to promotion strategies and the decision to buy sports products
Authors: Izadi Behzad , Ghaedi Ali , Ghasemian Mohammadreza
Published: September 2021

Purpose

Neuromarketing is a science that can examine human subconscious decisions and activities. The study aimed to investigate the neuropsychological responses of consumers to promotion strategies and the decision to buy sports products, in order to determine the more effective strategy.

Design/methodology/approach

An experimental design clarifies whether there is a significant difference between the neuropsychological responses resulting from selective promotional strategies (charity, endorsement, advertising and discount). The authors conducted the research with 40 young adults (20 males and 20 females; age range 25–35 years). The Enobio 20-channel electroencephalograph (EEG) is used to record waves, a two-item questionnaire is used to measure purchasing decisions and self-assessment forms are used to measure arousal and pleasure. Data analysis performed by Friedman's statistical methods and logistic regression using SPSS 22 software.

Findings

Based on the alpha wave, the results showed the two charity and endorsement strategies had the highest effect on consumer attentions. The pleasure had the highest value in the discount, and the arousal had the highest value in the charity strategy. Neuropsychological responses also explain a significant percentage of the consumer decision to buy.

Research limitations/implications

Access to research samples is difficult due to the ignorance of the samples as well as the fear of possible harm from imaging and brain scanning methods.

Practical implications

Neuromarketing is a science that can examine human subconscious decisions and activities.

Social implications

The information obtained neural methods are more accurate than traditional research methods.

Originality/value

This study showed the alpha brainwave (attention), arousal and pleasure explain a significant part of the consumer decision to buy. More scientific data can be obtained through new scientific approaches such as neuromarketing, which has a great impact on understanding consumer behavior. Therefore, marketers and researchers can make their promotional activities more effective in terms of them.