bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between faecal chemical pollutants and hormones in primates inhabiting Kibale National Park, Uganda
Authors: Steiniche Tessa , Wang Shaorui , Chester Emily , Mutegeki Richard , Rothman Jessica M. , Wrangham Richard W. , Chapman Colin A. , Venier Marta , Wasserman Michael D.
Published: May 2023

While anthropogenic pollutants are known to be a threat to primates, our understanding of exposure to pollutants
in situ
and their sub-lethal effects is still limited. We used non-invasive biomonitoring to examine associations between faecal concentrations of 97 chemical pollutants and faecal hormone metabolites of cortisol and oestradiol in four primate species inhabiting Kibale National Park, Uganda (chimpanzees—
Pan troglodytes
, olive baboons—
Papio anubis
, red colobus—
Piliocolobus tephrosceles
and red-tailed monkeys—
Cercopithecus ascanius
). Across all species (
n
= 71 samples), results demonstrated positive associations of organochlorine pesticides (OCPs) (
β
= 0.143,
p
= 0.020) and organophosphate esters (
β
= 0.112,
p
= 0.003) with cortisol in adult females. Additionally, we observed positive associations of OCPs (
β
= 0.192,
p
= 0.013) and brominated flame retardants (
β
= 0.176,
p
= 0.004) with cortisol in juveniles. Results suggest that cumulative pesticides and flame retardants are disruptive to endocrine function in these populations, which could have implications for development, metabolism and reproduction. Our study further demonstrates that faeces can be an important, non-invasive matrix for examining pollutant–hormone associations in wild primates and other critical wildlife populations.
Inter-species stimulus enhancement: herring gulls (
Larus argentatus
) mimic human food choice during foraging
Authors: Hacker Franziska , Smith Kiera , Graham Paul
Published: May 2023

Herring gulls (
Larus argentatus
) are one of few species that thrive in anthropogenic landscapes, and their familiarity with people makes them an excellent target for studies of inter-species social cognition. Urban gulls pay attention to human behaviour in food-related contexts and, thus, we set out to investigate whether such cues can influence a gull's attention to and choice of potential food items in their environment. Herring gulls were given free choice of two differently coloured anthropogenic food items in the presence of a demonstrator, who was either sitting still or eating food from an item that matched one of the presented ones. We found that a demonstrator eating significantly increased the likelihood of a gull pecking one of the presented items. Furthermore, 95% of pecks were directed toward the presented food item that colour-matched the demonstrator's food item. The results showed gulls were able to use human cues for stimulus enhancement and foraging decisions. Given the relatively recent history of urbanization in herring gulls, this cross-species social information transfer could be a by-product of the cognitive flexibility inherent in kleptoparasitic species.
A circuit analogy based girth growth model for living architecture design
Authors: Shu Qiguan , Ludwig Ferdinand
Published: May 2023

Architecture with and from living trees (Baubotanik) is a promising approach to sustainable, climate-adapted construction. Shaping and grafting allows one to create resilient structures that combine the ecological performance and aesthetics of trees with the functions of buildings. In order to design and engineer such living structures, it is necessary to predict the growth of different tree segments, especially when trunks, branches or roots are bent and jointed into a complex inosculated network. To address this, we have developed a tool to forecast the relative girth growth of different segments in such structures based on topological skeletons, the pipe model theory and circuit analogy. We have validated our results with a set of (scaled) photographs of inosculated tree structures of the so-called ‘Tree Circus’, covering over 80 years of their growth. Our model has proven to predict the relative girth growth with sufficient accuracy for conceptual design purposes. So far, it does not allow the simulation of absolute growth in circumference over the course of time that is necessary to predict quantitative technical aspects, such as mechanical performance at a given time. We conclude by briefly outlining how this could be addressed in future research.
Whole-genome sequencing and transcriptome-characterized in vitro evolution of aminoglycoside resistance in Mycobacterium tuberculosis
Authors: Wei Wenjing , Zhao Yuchuan , Zhang Chenchen , Yu Meiling , Wu Zhuhua , Xu Liuyue , Peng Kehao , Wu Zhilong , Li Yanxia , Wang Xuezhi
Published: May 2023

Antibiotic resistance of

Mycobacterium tuberculosis

(Mtb) is a major public health concern worldwide. Therefore, it is of great significance to characterize the mutational pathways by which susceptible Mtb evolves into drug resistance. In this study, we used laboratory evolution to explore the mutational pathways of aminoglycoside resistance. The level of resistance in amikacin inducing Mtb was also associated with changes in susceptibility to other anti-tuberculosis drugs such as isoniazid, levofloxacin and capreomycin. Whole-genome sequencing (WGS) revealed that the induced resistant Mtb strains had accumulated diverse mutations. We found that rrs A1401G was the predominant mutation in aminoglycoside-resistant clinical Mtb isolates from Guangdong. In addition, this study provided global insight into the characteristics of the transcriptome in four representative induced strains and revealed that rrs mutated and unmutated aminoglycoside-resistant Mtb strains have different transcriptional profiles. WGS analysis and transcriptional profiling of Mtb strains during evolution revealed that Mtb strains harbouring rrs A1401G have an evolutionary advantage over other drug-resistant strains under the pressure of aminoglycosides because of their ultra-high resistance level and low physiological impact on the strain. The results of this study should advance our understanding of aminoglycoside resistance mechanisms.
Long read genome assemblers struggle with small plasmids
Authors: Johnson Jared , Soehnlen Marty , Blankenship Heather M.
Published: May 2023

Whole-genome sequencing has become a preferred method for studying bacterial plasmids, as it is generally assumed to capture the entire genome. However, long-read genome assemblers have been shown to sometimes miss plasmid sequences – an issue that has been associated with plasmid size. The purpose of this study was to investigate the relationship between plasmid size and plasmid recovery by the long-read-only assemblers, Flye, Raven, Miniasm, and Canu. This was accomplished by determining the number of times each assembler successfully recovered 33 plasmids, ranging from 1919 to 194 062 bp in size and belonging to 14 bacterial isolates from six bacterial genera, using Oxford Nanopore long reads. These results were additionally compared to plasmid recovery rates by the short-read-first assembler, Unicycler, using both Oxford Nanopore long reads and Illumina short reads. Results from this study indicate that Canu, Flye, Miniasm, and Raven are prone to missing plasmid sequences, whereas Unicycler was successful at recovering 100 % of plasmid sequences. Excluding Canu, most plasmid loss by long-read-only assemblers was due to failure to recover plasmids smaller than 10 kb. As such, it is recommended that Unicycler be used to increase the likelihood of plasmid recovery during bacterial genome assembly.
Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors
Authors: Gaurav Amit , Bakht Perwez , Saini Mahak , Pandey Shivam , Pathania Ranjana
Published: May 2023

The problem of antibiotic resistance among pathogenic bacteria has reached a crisis level. The treatment options against infections caused by multiple drug-resistant bacteria are shrinking gradually. The current pace of the discovery of new antibacterial entities is lagging behind the rate of development of new resistance. Efflux pumps play a central role in making a bacterium resistant to multiple antibiotics due to their ability to expel a wide range of structurally diverse compounds. Besides providing an escape from antibacterial compounds, efflux pumps are also involved in bacterial stress response, virulence, biofilm formation, and altering host physiology. Efflux pumps are unique yet challenging targets for the discovery of novel efflux pump inhibitors (EPIs). EPIs could help rejuvenate our currently dried pipeline of antibacterial drug discovery. The current article highlights the recent developments in the field of efflux pumps, challenges faced during the development of EPIs and potential approaches for their development. Additionally, this review highlights the utility of resources such as natural products and machine learning to expand our EPIs arsenal using these latest technologies.
Reliability of force plate-based measures of standing balance in the sub-acute stage of post-stroke recovery
Authors: Aryan Raabeae , Inness Elizabeth , Patterson Kara K. , Mochizuki George , Mansfield Avril
Published: May 2023

Background

Difficulty controlling balance is one of the major contributors to the increased risk of falls among individuals with stroke. It is important to use reliable and objective measures to evaluate balance impairments post-stroke to inform more effective post-stroke rehabilitation.

Objectives

To examine the relative and absolute reliabilities of force plate-based balance measures in quiet standing, in the sub-acute stage of stroke recovery.

Methods

Twenty-four people with sub-acute stroke (mean age=61 years) performed two trials of quiet standing, each 30 seconds long. Sixteen force plate-based balance measures in the time, frequency, or nonlinear domains were calculated. Within-session test-retest reliabilities were investigated using intraclass correlation coefficient (ICC), standard error of measurement, and minimal detectable change.

Results

Mean speed of displacements of the centre of pressure along the anterior-posterior axis (ICC=0.91; CI95%=[0.83, 0.95]), and directional weight-bearing asymmetry (ICC=0.91; CI95%=[0.82, 0.95]) demonstrated high relative reliabilities, followed by the speed-based symmetry index and absolute weight-bearing asymmetry (both ICCs=0.86; CI95%=[0.74, 0.93]).

Conclusions

Mean speeds of centre of pressure, directional weight-bearing asymmetry, and speed-based symmetry index are the most reliable measures that can be included in the balance assessments of individuals within the sub-acute stage of post-stroke recovery. These findings can better inform clinicians about the specific balance problems experienced by people in this population.
Improvement of language function after Contralateral Seventh Cervical Nerve Transfer in hemiplegic patients combined with post-stroke aphasia: a prospective observational cohort study
Authors: Feng Juntao , Li Tie , Lv Minzhi , Xu Miaomiao , Yang Jingrui , Su Fan , Hu Ruiping , Li Jie , Shen Yundong , Xu Wendong
Published: May 2023

Background

While the contralateral seventh cervical nerve (CC7) cross transfer was designed to reconstruct paralyzed arm function after stroke, improvement in language function was found in patients combined with aphasia.

Objective

To evaluate the effect of improvement in language function after CC7 cross transfer in stroke patients with chronic aphasia and explore its potential mechanism.

Methods

In a prospective observative cohort, patients diagnosed with hemiplegia combined with aphasia were included. The language function was evaluated through the changes of Aphasia Quotient evaluated by Western Aphasia Battery (WAB-AQ) as well as its four subtests from baseline to 1 week and 6 months after the surgery. Patients also received oral agility test by Boston Diagnostic Aphasia Examination (BDAE-OA). Resting-state functional MRI (rs-fMRI) was scanned before and over 6 months after the surgery to explore the potential central mechanism in language improvements.

Results

The average increase of WAB-AQ was 8.08 points from baseline to 1 week post-operatively (P<0.001, 95%CI: 5.05-11.10), and 9.51 from baseline to 6-month (P<0.001, 95%CI: 6.75-12.27). In 8 patients who participant in BDAE-OA, the average increase was 3.7 points (95%CI: 0.56-6.84; corrected P =0.023) from baseline to 1-week follow-up, and 5.3 points from baseline to 6 months follow-up. Significant higher local activity was detected at right precentral cortex, right gyrus rectus, and right anterior cingulate cortex after the surgery from rs-fMRI.

Conclusions

Immediate and stable improvement in language function was detected after CC7 cross transfer in hemiplegic patients combined with aphasia, which may be realized through enhanced function of language network in the bilateral hemisphere.
Synthetic data for privacy-preserving clinical risk prediction
Authors: Qian Zhaozhi , Callender Thomas , Cebere Bogdan , Janes Sam M , Navani Neal , van der Schaar Mihaela
Published: May 2023

Synthetic data promise privacy-preserving data sharing for healthcare research and development. Compared with other privacy-enhancing approaches - such as federated learning - analyses performed on synthetic data can be applied downstream without modification, such that synthetic data can act in place of real data for a wide range of use cases. However, the role that synthetic data might play in all aspects of clinical model development remains unknown. In this work, we used state-of-the-art generators explicitly designed for privacy preservation to create a synthetic version of the UK Biobank before building prognostic models for lung cancer under several data release assumptions. We demonstrate that synthetic data can be effectively used throughout the modelling pipeline even without eventual access to the real data. Furthermore, we show the implications of different data release approaches on how synthetic data could be deployed within the healthcare system.
Left atrial strain in multisystem inflammatory syndrome in children (MIS-C) and associations with systemic inflammation and cardiac injury
Authors: Jepson Bryan M. , Beaver Matthew , Colquitt John L. , Truong Dongngan T. , Crandall Hillary , McFarland Carol , Williams Richard , Ou Zhining , Jensen Devri , Minich L. LuAnn , Binka Edem
Published: May 2023

Background

Multisystem inflammatory syndrome in children (MIS-C) commonly involves cardiac injury with both systolic and diastolic dysfunction. Left atrial strain (LAS) detects subclinical diastolic dysfunction in adults but is infrequently used in children. We evaluated LAS in MIS-C and the associations with systemic inflammation and cardiac injury.

Methods

In this retrospective cohort study, conventional parameters and LAS (reservoir [LAS-r], conduit [LAS-cd], and contractile [LAS-ct]) obtained from admission echocardiograms of MIS-C patients were compared to healthy controls and between MIS-C patients with and without cardiac injury (BNP >500 pg/ml or troponin-I >0.04 ng/ml). Correlation and logistic regression analyses were performed to assess LAS associations with admission inflammatory and cardiac biomarkers. Reliability testing was performed.

Results

Median LAS components were reduced in MIS-C patients (n=118) compared to controls (n=20) (LAS-r: 31.8 vs. 43.1%, p<0.001; LAS-cd: -28.8 vs. -34.5%, p=0.006; LAS-ct: -5.2 vs. -9.3%, p<0.001) and reduced in MIS-C patients with cardiac injury (n=59) compared to no injury (n=59) (LAS-r: 29.6 vs. 35.8%, p=0.001; LAS-cd: -26.5 vs. -30.4%, p=0.036; LAS-ct: -4.6 vs. -9.3%, p=0.008). An LAS-ct peak was absent in 65 (55%) MIS-C patients but present in all controls (p<0.001). Procalcitonin had strong correlation with averaged E/e’ (r=0.55, p=0.001); ESR had moderate correlation with LAS-ct (r=-0.41, p=0.007); BNP had moderate correlation with LAS-r (r=-0.39, p<0.001) and LAS-ct (r=0.31, p=0.023), and troponin-I had only weak correlations. No strain indices were independently associated with cardiac injury on regression analysis. Intra-rater reliability was good for all LAS components; and inter-rater reliability was good to excellent for LAS-r, and fair for LAS-cd and LAS-ct.

Conclusions

LAS analysis, particularly the absence of a LAS-ct peak, was reproducible and may be superior to conventional echocardiographic parameters for detecting diastolic dysfunction in MIS-C. No strain parameters on admission were independently associated with cardiac injury.
Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states
Authors: Aggarwal Adeeti , Luo Jennifer , Chung Helen , Contreras Diego , Kelz Max B. , Proekt Alex
Published: May 2023

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness stimuli evoke perceptions; under anesthesia perceptions are abolished; during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perception. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia and during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is elicited by specifically by external visual stimuli.
A variational autoencoder trained with priors from canonical pathways increases the interpretability of transcriptome data
Authors: Liu Bin , Rosenhahn Bodo , Illig Thomas , DeLuca David S.
Published: May 2023

Interpreting transcriptome data is an important yet challenging aspect of bioinformatic analysis. While gene set enrichment analysis is a standard tool for interpreting regulatory changes, we utilize deep learning techniques, specifically autoencoder architectures, to learn latent variables that drive transcriptome signals. We investigate whether simple, variational autoencoder (VAE), and beta-weighted VAE are capable of learning reduced representations of transcriptomes that retain critical biological information. We propose a novel VAE which utilizes priors from biological data to direct the network to learn a representation of the transcriptome that is based on understandable biological concepts.

After training five different autoencoder architectures on 22310 transcriptomes, we benchmarked their performance on organ and disease classification tasks on separate selection of 5577 test samples. Every tested architecture succeeded in reducing the transcriptomes to 50 latent dimensions, which captured enough variation for accurate reconstruction. The simple, fully connected autoencoder, performs best across the benchmarks, but lacks the characteristic of having directly interpretable latent dimensions. The beta-weighted, prior-informed VAE implementation is able to solve the benchmarking tasks, and provide semantically accurate latent features equating to biological pathways.

This study opens a new direction for differential pathway analysis in transcriptomics with increased transparency and interpretability.

Author summary

The ability to measure the human transcriptome has been a critical tool to studying health and disease. However, transcriptomes data sets are too large and complex for direct human interpretation. Deep learning techniques such as autoencoders are capable of distilling high-level features from complex data. However, even if deep learning models find patterns, these patterns are not necessarily represented in a way that humans can easily understand. By bringing in the prior knowledge of biological pathways, we have trained the model to “speak the language” of the biologist, and represent complex transcrtomes, in simpler concepts that are already familiar to biologists. We can then apply the tool to compare for example samples from lung cancer cells to healthy cells, and show which biological processes are perturbed.
Identification of immune-related genes for the diagnosis of ischaemic heart failure based on bioinformatics and three machine learning models
Authors: Yu Yi-ding , Xue Yi-tao , Li Yan
Published: May 2023

Background

The role of immune cells in the pathogenesis of ischaemic heart failure (IHF) is well-established. However, identifying key diagnostic candidate genes in patients with IHF remains a challenge. Therefore, this study aimed to use bioinformatics and machine learning algorithms to identify potential diagnostic genes for IHF.

Methods

Two IHF datasets were obtained from the GEO database, and key genes for IHF were identified using Limma and WGCNA. Functional enrichment analysis was performed to explore the potential mechanisms of IHF. Next, we used three machine learning algorithms, namely LASSO, RF, and SVM-REF, to identify immune-related diagnostic genes for IHF. ssGSEA enrichment analysis was also completed. To assess the diagnostic value of the identified genes, we developed nomogram and validated them on additional GEO datasets. Finally, an immune infiltration analysis was conducted using the CIBERSORT algorithm to explore immune cell dysregulation in IHF.

Results

Our analysis yielded a total of 92 key genes associated with IHF. Enrichment analysis revealed that the mechanisms underlying IHF are mostly associated with immunity and inflammation. Using the machine learning algorithms, we identified four IHF diagnostic genes, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets. The results showed that these four genes had high diagnostic value (AUC value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely Macrophages M2, Monocytes, and T cells gamma delta.

Conclusion

In summary, our study identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms. We also explored the potential molecular mechanisms of IHF and the immune cell infiltration environment of the failing myocardium. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF.
Neo-functionalization and co-option of Pif genes facilitate the evolution of a novel shell microstructure in oysters
Authors: Bai Yitian , Liu Shikai , Hu Yiming , Yu Hong , Kong Lingfeng , Xu Chengxun , Li Qi
Published: May 2023

Molluscan shell, composed of a diverse range of architectures and microstructures, is a classic model system to study the relationships between molecular evolution and biomineralized structure formation. The shells of oysters differ from those of other molluscs by possessing a novel microstructure, chalky calcite, which facilitates adaptation to the sessile lifestyle. However, the genetic basis and evolutionary origin of this adaptive innovation remain largely unknown. Here, we present the first chromosome-level genome and shell proteomes of the Iwagaki oysterCrassostrea nippona. Multi-omic integrative analyses revealed that independently evolved and co-opted genes as well as lineage-specific domains are involved in the formation of chalky layer in the oysters. Rapid mineralization involving chalky calcite are essential for reconstruction of the shell. Importantly, von Willebrand factor type A and chitin-binding domains are identified as basic members of molluscan biomineralization toolkit. We show that the well-known Pif shared a common origin in the last common ancestor of Bilateria. Furthermore, Pif and LamG3 genes acquire new genetic function for shell mineralization in bivalves and the chalky layer formation in oysters through a combination of gene duplication and domain reorganization. Our findings highlight neo-functionalization as a crucial mechanism for shell diversity, which may be applied more widely for studies on the evolution of metazoan biomineralization. This study also has potential implications for material science and biomimetic research.
Formation of a stable RNase Y-RicT (YaaT) complex requires RicA (YmcA) and RicF (YlbF)
Authors: Dubnau Eugenie , DeSantis Micaela , Dubnau David
Published: May 2023

InBacillus subtilis, the RicT (YaaT), RicA (YmcA) and RicF (YlbF) proteins, which form a stable ternary complex, are needed together with RNase Y (Rny), to cleave and thereby stabilize several key transcripts encoding enzymes of intermediary metabolism. We show here that RicT, but not RicA or RicF, forms a stable complex with Rny, and that this association requires the presence of RicA and RicF. We propose that RicT is handed off from the ternary complex to Rny. We show further that the two iron-sulfur clusters carried by the ternary Ric complex are required for the formation of the stable RicT-Rny complex. We demonstrate that proteins of the degradosome-like network ofB. subtilis, which also interact with Rny, are dispensable for processing of thegapAoperon. Thus, Rny participates in distinct RNA-related processes, determined by its binding partners, and a RicT-Rny complex is likely the functional entity forgapAmRNA maturation.

IMPORTANCE

The action of nucleases on RNA is universal and essential for all forms of life and includes processing steps that lead to the mature and functional forms of certain transcripts. InB. subtilisit has been shown that key transcripts for energy producing steps of glycolysis, for nitrogen assimilation and for oxidative phosphorylation, all of them crucial processes of intermediary metabolism, are cleaved at specific locations, resulting in mRNA stabilization. The proteins required for these cleavages inB. subtilis(Rny (RNase Y), RicA (YmcA), RicF (YlbF) and RicT (YaaT)) are broadly conserved among the firmicutes, including in several important pathogens, hinting that regulatory mechanisms they control may also be conserved. Several aspects of these regulatory events have been explored: phenotypes associated with the absence of these proteins have been described, the impact of these absences on the transcriptome has been documented, and there has been significant exploration of the biochemistry and structural biology of Rny and the Ric proteins. The present study further advances our understanding of the association of Ric proteins and Rny and shows that a complex of Rny with RicT is probably the entity that carries out mRNA maturation.
Effects of focused ultrasound in a “clean” mouse model of ultrasonic neuromodulation
Authors: Guo Hongsun , Salahshoor Hossein , Wu Di , Yoo Sangjin , Sato Tomokazu , Tsao Doris Y. , Shapiro Mikhail G.
Published: May 2023

Recent studies on ultrasonic neuromodulation (UNM) in rodents have shown that focused ultrasound (FUS) can activate peripheral auditory pathways, leading to off-target and brain-wide excitation, which obscures the direct activation of the target area by FUS. To address this issue, we developed a new mouse model, the double transgenic Pou4f3+/DTR × Thy1-GCaMP6s, which allows for inducible deafening using diphtheria toxin and minimizes off-target effects of UNM while allowing effects on neural activity to be visualized with fluorescent calcium imaging. Using this model, we found that the auditory confounds caused by FUS can be significantly reduced or eliminated within a certain pressure range. At higher pressures, FUS can result in focal fluorescence dips at the target, elicit non-auditory sensory confounds, and damage tissue, leading to spreading depolarization. Under the acoustic conditions we tested, we did not observe direct calcium responses in the mouse cortex. Our findings provide a cleaner animal model for UNM and sonogenetics research, establish a parameter range within which off-target effects are confidently avoided, and reveal the non-auditory side effects of higher-pressure stimulation.
Spatiotemporal modulation of a fixed set of muscle synergies during unpredictable and predictable gait perturbations in older adults
Authors: Brüll Leon , Santuz Alessandro , Mersmann Falk , Bohm Sebastian , Schwenk Michael , Arampatzis Adamantios
Published: May 2023

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed and the recovery steps. Sixty-three healthy older adults (71.2 ± 5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (p<0.05). These modifications were observed up to four recovery steps and were more pronounced (p<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may facilitate the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.

Summary statement

The flexible recruitment of the four and well-known muscle synergies responsible for unperturbed walking during unpredictable and predictable gait perturbations indicates an effective way to counteract locomotor perturbations, where fast reactive responses are necessary to maintain postural stability.
PHOSPHORYLATION OF RyR2 SIMULTANEOUSLY EXPANDS THE DYAD AND REARRANGES THE TETRAMERS
Authors: Asghari Parisa , Scriven David R.L. , Shahrasebi Saba , Valdivia Hector H. , Wehrens Xander H.T. , Moore Edwin D.W.
Published: May 2023

We have previously demonstrated that type II ryanodine receptors (RyR2) tetramers can be rapidly rearranged in response to a phosphorylation cocktail. The cocktail modified downstream targets indiscriminately making it impossible to determine whether phosphorylation of RyR2 was an essential element of the response. We therefore used the β-agonist isoproterenol and mice with one of the homozygous mutations, S2030A+/+, S2808A+/+, S2814A+/+, or S2814D+/+, to address this question and to elucidate the role of these clinically relevant mutations. We measured the length of the dyad using transmission electron microscopy (TEM) and directly visualized RyR2 distribution using dual-tilt electron tomography. We found that: 1) The S2814D mutation, by itself, significantly expanded the dyad and reorganized the tetramers suggesting a direct link between the phosphorylation state of the tetramer and the microarchitecture. 2) All of the wild-type, as well as the S2808A and S2814A mice, had significant expansions of their dyads in response to ISO, while S2030A did not. 3) In agreement with functional data from the same mutants, S2030 and S2808 were necessary for a complete β-adrenergic response, whereas S2814 was not. 4) All the mutated residues had unique effects on the organization of their tetramer arrays. 5) The correlation of structure with function suggests that tetramer-tetramer contacts play an important functional role. We conclude that both the size of the dyad and the arrangement of the tetramers are linked to the state of the channel tetramer and can be dynamically altered by a β-adrenergic receptor agonist.

Analysis of RyR2 mutants suggests a direct link between the phosphorylation state of the channel tetramer and the microarchitecture of the dyad. All phosphorylation site mutations produced significant and unique effects on the structure of the dyad and its response to isoproterenol.
Guild-level response of the gut microbiota to isocaloric time-restricted feeding in high-fat diet-fed mice
Authors: Ghosh Shreya , Li Yue , Yang Xin , Wu Guojun , Zhang Chenhong , Zhao Liping
Published: May 2023

Time-restricted feeding (TRF) during the active phase protects against high-fat diet (HFD)-induced obesity, and its impact on gut microbiota has been previously investigated using bacterial taxa as functional units. However, in the gut ecosystem, bacteria from different taxonomic backgrounds form coherent functional groups called guilds, whose members exhibit co-abundant behavior. Thirty-five co-abundance groups (CAGs), clustered from 297 prevalent amplicon sequence variants (ASVs), showed greater concordance with beta-diversity plots based on all 1131 ASVs than the 130 classifiable genera, leading to a significantly improved preservation of community-level information. TRF-enriched CAGs positively correlated with metabolic improvement, while TRF-reduced CAGs negatively correlated. TRF restored the diurnal rhythm of most of these key CAGs. Novel ASVs, unclassifiable at the genus level, were identified in these key CAGs. Overall, this suggests that the key bacterial guilds may mediate the beneficial metabolic effects of TRF through the restoration of diurnal oscillation.
Employing Deep Learning Model to Evaluate Speech Information in Vocoder Simulations of Auditory Implants
Authors: Sinha Rahul , Azadpour Mahan
Published: May 2023

Vocoder simulations have played a crucial role in the development of sound coding and speech processing techniques for auditory implant devices. Vocoders have been extensively used to model the effects of implant signal processing as well as individual anatomy and physiology on speech perception of implant users. Traditionally, such simulations have been conducted on human subjects, which can be time-consuming and costly. In addition, perception of vocoded speech varies significantly across individual subjects, and can be significantly affected by small amounts of familiarization or exposure to vocoded sounds. In this study, we propose a novel method that differs from traditional vocoder studies. Rather than using actual human participants, we use a speech recognition model to examine the influence of vocoder-simulated cochlear implant processing on speech perception. We used the OpenAI Whisper, a recently developed advanced open-source deep learning speech recognition model. The Whisper model’s performance was evaluated on vocoded words and sentences in both quiet and noisy conditions with respect to several vocoder parameters such as number of spectral bands, input frequency range, envelope cut-off frequency, envelope dynamic range, and number of discriminable envelope steps. Our results indicate that the Whisper model exhibited human-like robustness to vocoder simulations, with performance closely mirroring that of human subjects in response to modifications in vocoder parameters. Furthermore, this proposed method has the advantage of being far less expensive and quicker than traditional human studies, while also being free from inter-individual variability in learning abilities, cognitive factors, and attentional states. Our study demonstrates the potential of employing advanced deep learning models of speech recognition in auditory prosthesis research.
Detailed Survey of an in-vitro Intestinal Epithelium Model by Single-Cell Transcriptomics
Authors: Ran Ran , Munoz Javier , Jena Smrutiti , Green Leopold N. , Brubaker Douglas K.
Published: May 2023

The gut plays a critical role in maintaining human health by facilitating the absorption of nutrients, regulating metabolism, and interacting with the immune system and gut microbiota. The co-culture of two human colorectal cancer cell lines, Caco-2 and HT29, on Transwell is commonly used as anin vitrogut mimic in studies of intestinal absorption pharmacokinetics, gut mechanics, and gut-microbe interplay given the similar morphology, expression of transporters and enzymes, and barrier function. However, to sufficiently evaluate the translatability of insights from such a system to human physiological contexts, a detailed survey of cell type heterogeneity in the system and a holistic comparison with human physiology are needed to be conducted rather than by the presence of a few well-studied proteins. Single-cell RNA sequencing provides high-resolution expression profiles of cells in the co-culture, enabling the heterogeneity to be characterized and the similarity to human epithelial cells to be evaluated. Transcriptional profiles of 16019 genes in 13784 cells were acquired and compared to human epithelial cells (GSE185224). We identified the intestinal stem cell-, transit amplifying-, enterocyte-, goblet cell-, and enteroendocrine-like cells together with differentiating HT29 cells in the system based on the expression of canonical markers in healthy adult human epithelial cells. The epithelium-like co-culture was fetal intestine-like, with less variety of gene expression compared to the human gut. Transporters for major types of substance (lipid, amino acid, ion, water, etc.) were found transcribed in the majority of the enterocytes-like cells in the system. However, some of the well-studied transporters such as FATP4 and GLUT2 were absent. Toll-like receptors were not highly expressed in the sample, yet the treatment of lipopolysaccharide still caused a mild change in trans-epithelial electrical resistance and gene expression, possibly by the interaction with CD14, the co-receptor for TLRs. Overall, the Caco-2/HT29 co-culture is a cost-effective epithelium model for drug permeability testing or mechanical simulation, but its phenotypic discrepancy with the real epithelium is not negligible. As a result, its response to biological factors might not provide transferrable knowledge to the study of human gut physiology, especially the innate immune aspect.
Simultaneous carbon catabolite repression governs sugar and aromatic co-utilization inPseudomonas putidaM2
Authors: Shrestha Shilva , Awasthi Deepika , Chen Yan , Gin Jennifer , Petzold Christopher J. , Adams Paul D. , Simmons Blake A. , Singer Steven W.
Published: May 2023

Pseudomonas putidahave emerged as promising biocatalysts for the conversion of sugars and aromatics obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning inP. putidaM2, a strain capable of consuming both hexose and pentose sugars as well as aromatics, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatics simultaneously; however, during co-cultivation with glucose and phenylpropanoid aromatics (p-coumarate and ferulate), intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during co-cultivation with aromatics implying simultaneous catabolite repression by sugars and aromatics. Downregulation ofcrcvia CRISPRi led to faster growth and uptake of glucose andp-coumarate in the CRISPRi strains compared to the control while no difference was observed on xylose +p-coumarate. The increased abundance of the Eda and amino acids biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified inP. putidastrains, were lower under strong CCR (glucose +p-coumarate) condition compared to when repression was absent (p-coumarate or glucose only).

IMPORTANCE

A newly isolatedPseudomonas putidastrain,P. putidaM2, can utilize both hexose and pentose sugars as well as aromatics making it a promising host for the valorization of lignocellulosic biomass. Pseudomonads have developed a regulatory strategy, carbon catabolite repression, to control the assimilation of carbon sources in the environment. Carbon catabolite repression may impede the simultaneous and complete metabolism of sugars and aromatics present in lignocellulosic biomass and hinder the development of an efficient industrial biocatalyst. This study provides insight into the cellular physiology and proteome during mixed-substrate utilization inP. putidaM2. The phenotypic and proteomics results demonstrated simultaneous catabolite repression in the sugar-aromatic mixtures while the CRISPRi and sRNA sequencing demonstrated the potential role of thecrcgene and small RNAs in carbon catabolite repression.
Live tracking of a plant pathogen outbreak reveals rapid and successive, multidecade episome reduction
Authors: Roman-Reyna Veronica , Sharma Anuj , Toth Hannah , Konkel Zachary , Omiotek Nicolle , Murthy Shashanka , Faith Seth , Slot Jason , Hand Francesca Peduto , Goss Erica , Jacobs Jonathan M.
Published: May 2023

Quickly understanding the genomic changes that lead to pathogen emergence is necessary to launch mitigation efforts and reduce harm. Often the evolutionary events that result in an epidemic typically remain elusive long after an outbreak, which is particularly true for plant pathogens. To rapidly define the consequential evolutionary events result in pathogen emergence, we tracked in real-time a 2022 bacterial plant disease outbreak in US geranium (Pelargoniumxhortorum) caused by Xhp2022, a novel lineage ofXanthomonas hortorum. Genomes from 31 Xhp2022 isolates from seven states showed limited chromosomal variation, and all contained a single plasmid (p93). Time tree and SNP whole genome analysis estimated that Xhp2022 emerged in the early 2020s. Phylogenomic analysis determined that p93 resulted from cointegration of three plasmids (p31, p45, and p66) present in a 2012 outbreak. p31, p45 and p66 were individually found in varying abundance acrossX. hortorumisolates from historical outbreaks dating to 1974 suggesting these plasmids were maintained in the broader metapopulation. p93 specifically arose from two co-integration events from homologous and Tn3and XerC-mediated site-specific recombination. Although p93 suffered a 49kb nucleotide reduction, it maintained critical fitness gene functions encoding, for example, metal resistance and virulence factors, which were likely selected by the ornamental production system. Overall we demonstrate how rapid sequencing of current and historical isolates track the evolutionary history of an emerging, ongoing threat. We show a recent, tractable event of genome reduction for niche adaptation typically observed over millenia in obligate and fastidious pathogens.

Significance

Genome-resolved epidemiology is rapidly changing how we track pathogens in real-time to support stakeholders and health. This research highlights how we responded to a current disease outbreak of geranium. Our work revealed that a new group of the bacterial plant pathogenXanthomonas horotrumemerged in 2022 as a result of a recent genome reduction. We determined that three distinct plasmids were present in the broaderX. hortorummetapopulation since 1974. In 2012, the three plasmids were altogether present in individual isolates; then in 2022, all three plasmids co-integrated while maintaining critical fitness genes but losing extraneous genomic material. This parallels genome efficiency and reduction that we see across millenia or even millions of years with obligate parasites with increased niche-specificity.
High-pressure single-crystal diffraction at the Australian Synchrotron
Authors: Boer Stephanie A. , Price Jason R. , Riboldi-Tunnicliffe Alan , Williamson Rachel , Rostan Robert , Summers Aston , Turner Gemma F. , Jones Isabelle , Bond Charles S. , Vrielink Alice , Marshall Andrew C. , Hitchings John , Moggach Stephen A.
Published: May 2023

A new high-pressure single-crystal diffraction setup has been designed and implemented at the Australian Synchrotron for collecting molecular and protein crystal structures. The setup incorporates a modified micro-Merrill–Bassett cell and holder designed specifically to fit onto the horizontal air-bearing goniometer, allowing high-pressure diffraction measurements to be collected with little to no modification of the beamline setup compared with ambient data collections. Compression data for the amino acid, L-threonine, and the protein, hen egg-white lysozyme, were collected, showcasing the capabilities of the setup.
Effects of the cementite morphology on the hydrogen trapping behavior in the pipeline steel
Authors: Tu Yanqi , Liu Saiyu , Shi Rongjian , Yang Shani , Gao Kewei , Pang Xiaolu
Published: May 2023

Purpose

The purpose of this study is to investigate the effects of the cementite morphology on the hydrogen trapping behavior in low-alloy pipeline steel.

Design/methodology/approach

In this study, the hydrogen trapping behavior in low-alloy pipeline steel was quantitatively studied by a combination of microstructural observations, electrochemical hydrogen permeation experiments and thermal desorption spectroscopy (TDS) analyses.

Findings

P-1 and P-2 steels are two samples with different microstructures. The morphology of cementite precipitates in the P-1 and P-2 steels was different. Lamellar cementite is present in P-2 steel and only granular cementite in P-1 steel, which led to a better irreversible hydrogen trapping ability of P-2 steel, which was confirmed by subsequent hydrogen permeation and TDS experiments.

Originality/value

The study of these deep hydrogen trap sites is helpful in improving the hydrogen embrittlement resistance of low-alloy pipeline steels.
Blockchain: a promising technology for judicial translation services in cases with foreign elements
Authors: Huang Lingling , Zhao Chengqiang , Chen Shijie , Zeng Liujing
Published: May 2023

Purpose

Technical advantages embraced by blockchain, such as distributed ledger, P2P networks, consensus mechanisms and smart contracts, are highly compatible with addressing the security issues of transferring and storing judicial documents and obtaining the feedback and evaluation of judicial translation services in cases with foreign elements. Therefore, based on this, a consortium blockchain-based model for supervising the overall process of judicial translation services in cases with foreign elements is proposed.

Design/methodology/approach

Some judicial documents are required to be translated when there are language barriers in cases with foreign elements. The purpose of this paper is expected to address security issues, which is ignored, in the process of translating judicial documents.

Findings

The experimental results show that the model constructed in this paper can effectively guarantee the security and privacy of transferring and storing translated judicial documents in cases with foreign elements, and realize the credibility and traceability of feedbacks and evaluations of judicial translation services. In addition, the underlying network communications is stable and the speed for processing data can meet the requirements of practical application.

Originality/value

The research in this paper provides an innovative scheme for judicial translation services in cases with foreign elements. The model constructed is conducive to protecting the security of the transfer and storage of judicial documents and improving the efficiency and modernization ability of hearing cases with foreign elements.