bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing implementation of the GLA:D Back, an educational/exercise intervention for low back pain: a mixed-methods study
Authors: Ris Inge , Boyle Eleanor , Myburgh Corrie , Hartvigsen Jan , Thomassen Line , Kongsted Alice
Published: November 2021

Introduction and aims:

Guidelines for low back pain (LBP) management recommend patient education and exercises. GLA:D Back, a structured group-based patient-education exercise program for LBP, facilitates evidence-based care implementation. This study aimed to inform on the implementation processes, assessing clinician-related factors. Objectives were to describe profiles of implementers and nonimplementers by demographics, and responses to the tailored version of the Determinants of Implementation Behaviour Questionnaire (DIBQ-t) qualitatively explore clinician perspectives on implementation, and compare the results of the DIBQ-t with the interview data to evaluate their fit of integration for facilitators, barriers, and new insights.

Methods:

A mixed-methods parallel design study was conducted. Physiotherapists and chiropractors, educated in the GLA:D Back program, were asked to complete the DIBQ-t (measuring theoretical determinants of implementation) 6 months after their training. Implementers and nonimplementers of the program were selected for interviews. Qualitative data were used to understand clinicians’ viewpoints on implementation, providing a broader perspective on the quantitative data and exploring new aspects.

Results:

More physiotherapists than chiropractors implemented the program. Implementers responded more positively on most domains of the DIBQ-t. The interviews revealed three themes important for implementation: personal gain, practicalities, and buying-in on the program. Clinicians’ attitudes to the program appeared additionally as relevant to implementation.

Conclusion:

The profession of the clinician was associated with implementation behavior. Implementers and nonimplementers identified the same themes but perceived them as either positive or negative. Both groups reported high levels of knowledge and skills, indicating that training alone is insufficient for implementation.
Prevention of needle-stick injury among nurses in an acute ward of a hospital: a best practice implementation project
Authors: Huang Hui-Mei , Chien Hsing-Chin , Lin Wen-ling , Chang Chia-Hui , Chang Mei-Yu , Su Jui-Yuan , Mu Pei-Fan
Published: November 2021

Objectives:

This evidence implementation project aimed to identify barriers leading to needle-stick injuries (NSIs) and to develop implementation strategies to prevent NSIs in the acute ward of a hospital in central Taiwan.

Introduction:

The incidence rate of NSIs was 5.6% in the acute ward of a hospital in Taiwan. NSIs commonly occur during the drawing of blood, intravenous insertion, needle recapping, or performing any procedure involving sharp medical devices. NSIs are critical occupational risks among healthcare workers, possibly leading to transmission of infectious diseases, especially blood-borne viruses, such as HIV, hepatitis B, and hepatitis C.

Methods:

A clinical audit was undertaken using the JBI Practical Application of Clinical Evidence System (PACES) and the Getting Research into Practice (GRiP) approach. Five audit criteria that represented best practice recommendations for prevention of NSIs were used. Baseline data were collected from 177 nurses in five acute wards, followed by the implementation of multiple strategies during a 20-week period of the project. Both baseline and postimplementation audits were undertaken to determine changes in practice.

Results:

According to the pre-audit concerning the use of safety-engineered injection devices and safe use and disposal of needles, there was 14–15% compliance, which indicated poor compliance with current best-practice criteria. Following the project implementation, the nursing staff were educated about the well tolerated use and disposal of sharps and the improved compliance rate ranged from 40 to 96.6%, with safety needle use increasing from 16 to 95.5%, safety needle operation procedure awareness increasing from 14 to 96%, needles not recapped after use increasing from 47 to 85%, and placing used needles in the sharps collection box increasing from 75 to 80%.

Conclusion:

This article suggests that standardized puncture prevention education and training enhanced nurses’ awareness in the acute ward.
Pelvic floor muscle training in mother fit healthcare centres: a best practice implementation project
Authors: Ghaderi Fariba , Hajebrahimi Sakineh , Ghaderi Farzaneh , Pashazadeh Fariba
Published: November 2021

Introduction and aims:

Pelvic floor dysfunctions are common complications during the childbirth process. Pelvic floor muscle training (PFMT) has been used as a conservative treatment in both prenatal and postnatal women. The aim of this project was to assess the compliance with evidence-based criteria regarding PFMT among prenatal and postnatal women in mother fit healthcare centres.

Methods:

The current study was performed in three phases. Phase 1: stakeholder engagement and team establishment and baseline audit. Phase 2: Design and implementation of strategies to improve PFMT among prenatal and postnatal women in mother fit healthcare centres. Phase 3: Follow-up audit. Baseline and follow-up audit with six yes/no audit questions was performed using the Joanna Briggs Institute Practical Application of Clinical Evidence System. Fifteen midwives involved in prenatal and postnatal healthcare centres and 60 pregnant women participated in this study.

Results:

The compliance for each audit criterion found in the baseline audit was low (0–7%). However, after implementation of the project and training the trainers (midwives), the compliance increased significantly (77–100%).

Conclusion:

The current study demonstrated that we have some problems in the healthcare system to teach PFMT to pregnant women. We should also implement similar projects in all healthcare centres country wide. Healthcare system managers should be aware of the value of holding PFMT courses for pregnant women and it is recommended to use pelvic floor physiotherapists to train midwives.
Social convergence of gut microbiomes in vampire bats
Authors: Yarlagadda Karthik , Razik Imran , Malhi Ripan S. , Carter Gerald G.
Published: November 2021

The ‘social microbiome’ can fundamentally shape the costs and benefits of group-living, but understanding social transmission of microbes in free-living animals is challenging due to confounding effects of kinship and shared environments (e.g. highly associated individuals often share the same spaces, food and water). Here, we report evidence for convergence towards a social microbiome among introduced common vampire bats,Desmodus rotundus, a highly social species in which adults feed only on blood, and engage in both mouth-to-body allogrooming and mouth-to-mouth regurgitated food sharing. Shotgun sequencing of samples from six zoos in the USA, 15 wild-caught bats from a colony in Belize and 31 bats from three colonies in Panama showed that faecal microbiomes were more similar within colonies than between colonies. To assess microbial transmission, we created an experimentally merged group of the Panama bats from the three distant sites by housing these bats together for four months. In this merged colony, we found evidence that dyadic gut microbiome similarity increased with both clustering and oral contact, leading to microbiome convergence among introduced bats. Our findings demonstrate that social interactions shape microbiome similarity even when controlling for past social history, kinship, environment and diet.
The Twenty Item Prosopagnosia Index (PI20) provides meaningful evidence of face recognition impairment
Authors: Tsantani Maria , Vestner Tim , Cook Richard
Published: November 2021

The Twenty Item Prosopagnosia Index (PI20) is a self-report questionnaire used for quantifying prosopagnosic traits. This scale is intended to help researchers identify cases of developmental prosopagnosia by providing standardized self-report evidence to complement diagnostic evidence obtained from objective computer-based tasks. In order to respond appropriately to items, prosopagnosics must have some insight that their face recognition is well below average, while non-prosopagnosics need to understand that their relative face recognition ability falls within the typical range. There has been considerable debate about whether participants have the necessary insight into their face recognition abilities to respond appropriately. In the present study, we sought to determine whether the PI20 provides meaningful evidence of face recognition impairment. In keeping with the intended use of the instrument, we used PI20 scores to identify two groups: high-PI20 scorers (those with self-reported face recognition difficulties) and low-PI20 scorers (those with no self-reported face recognition difficulties). We found that participant groups distinguished on the basis of PI20 scores clearly differed in terms of their mean performance on objective measures of face recognition ability. We also found that high-PI20 scorers were more likely to achieve levels of face recognition accuracy associated with developmental prosopagnosia.
A comparative analysis of the mechanisms of ammonia synthesis on various catalysts using density functional theory
Authors: Zeinalipour-Yazdi Constantinos D. , Hargreaves Justin S. J. , Laassiri Said , Catlow C. Richard A.
Published: November 2021

In this review, we present the recent progress in ammonia synthesis research using density functional theory (DFT) calculations on various industrial catalysts, metal nitrides and nano-cluster-supported catalysts. The mechanism of ammonia synthesis on the industrial Fe catalyst is generally accepted to be a
dissociative mechanism
. We have recently found, using DFT techniques, that on Co
3
Mo
3
N (111) surfaces, an
associative mechanism
in the synthesis of ammonia can offer a new low-energy pathway that was previously unknown. In particular, we have shown that metal nitrides that are also known to have high activity for ammonia synthesis can readily form nitrogen vacancies which can activate dinitrogen, thereby promoting the associative mechanism. These fundamental studies suggest that a promising route to the discovery of low-temperature ammonia synthesis catalysts will be to identify systems that proceed via the associative mechanism, which is closer to the nitrogen-fixation mechanism occurring in nitrogenases.
A portable exotendon assisting hip and knee joints reduces muscular burden during walking
Authors: Cheng Longfei , Xiong Caihua , Chen Wenbin , Liang Jiejunyi , Huang Bo , Xu Xiaowei
Published: November 2021

Assistive devices are used to reduce human effort during locomotion with increasing success. More assistance strategies are worth exploring, so we aimed to design a lightweight biarticular device with well-chosen parameters to reduce muscle effort. Based on the experience of previous success, we designed an exotendon to assist in swing leg deceleration. Then we conducted experiments to test the performance of the exotendon with different spring stiffness during walking. With the assistance of the exotendon, peak activation of semitendinosus decreased, with the largest reduction of 12.3% achieved with the highest spring stiffness (p= 0.004). The peak activations of other measured muscles were not significantly different (p= 0.15–0.92). The biological hip extension and knee flexion moments likewise significantly decreased with the spring stiffness (p< 0.01). The joint angle was altered during the assisted phases with decreased hip flexion and knee extension. Meanwhile, the step frequency and the step length were also altered, while the step width remained unaffected. Gait variability changed only in the frontal plane, exhibiting lower step width variability. We conclude that passive devices assisting hip extension and knee flexion can significantly reduce the burden on the hamstring muscles, while the kinematics is easily altered.
Symplectic decomposition from submatrix determinants
Authors: Pereira Jason L. , Banchi Leonardo , Pirandola Stefano
Published: November 2021

An important theorem in Gaussian quantum information tells us that we can diagonalize the covariance matrix of any Gaussian state via a symplectic transformation. While the diagonal form is easy to find, the process for finding the diagonalizing symplectic can be more difficult, and a common, existing method requires taking matrix powers, which can be demanding analytically. Inspired by a recently presented technique for finding the eigenvectors of a Hermitian matrix from certain submatrix eigenvalues, we derive a similar method for finding the diagonalizing symplectic from certain submatrix determinants, which could prove useful in Gaussian quantum information.
Mitonuclear interactions alter sex-specific longevity in a species without sex chromosomes
Authors: Flanagan Ben A. , Li Ning , Edmands Suzanne
Published: November 2021

Impaired mitochondrial function can lead to senescence and the ageing phenotype. Theory predicts degenerative ageing phenotypes and mitochondrial pathologies may occur more frequently in males due to the matrilineal inheritance pattern of mitochondrial DNA observed in most eukaryotes. Here, we estimated the sex-specific longevity for parental and reciprocal F1 hybrid crosses for inbred lines derived from two allopatric
Tigriopus californicus
populations with over 20% mitochondrial DNA divergence.
T. californicus
lacks sex chromosomes allowing for more direct testing of mitochondrial function in sex-specific ageing. To better understand the ageing mechanism, we estimated two age-related phenotypes (mtDNA content and 8-hydroxy-20-deoxyguanosine (8-OH-dG) DNA damage) at two time points in the lifespan. Sex differences in lifespan depended on the mitochondrial and nuclear backgrounds, including differences between reciprocal F1 crosses which have different mitochondrial haplotypes on a 50 : 50 nuclear background, with nuclear contributions coming from alternative parents. Young females showed the highest mtDNA content which decreased with age, while DNA damage in males increased with age and exceed that of females 56 days after hatching. The adult sex ratio was male-biased and was attributed to complex mitonuclear interactions. Results thus demonstrate that sex differences in ageing depend on mitonuclear interactions in the absence of sex chromosomes.
Chimpanzees and bonobos use social leverage in an ultimatum game
Authors: Sánchez-Amaro Alejandro , Rossano Federico
Published: November 2021

The ultimatum game (UG) is widely used to investigate our sense of fairness, a key characteristic that differentiates us from our closest living relatives, bonobos and chimpanzees. Previous studies found that, in general, great apes behave as rational maximizers in the UG. Proposers tend to choose self-maximizing offers, while responders accept most non-zero offers. These studies do not rule out the possibility that apes can behave prosocially to improve the returns for themselves and others. However, this has never been well studied. In this study, we offer chimpanzee and bonobo proposers the possibility of taking into account the leverage of responders over the offers they receive. This leverage takes the form of access to alternatives for responders. We find that proposers tend to propose fairer offers when responders have the option to access alternatives. Furthermore, we find that both species use their leverage to reject unequal offers. Our results suggest that great apes mostly act as rational maximizers in an UG, yet access to alternatives can lead them to change their strategies such as not choosing the self-maximizing offer as proposers and not accepting every offer higher than zero as responders.
Effects of physical impairments on fitness correlates of the white-footed mouse,Peromyscus leucopus
Authors: Rubino Francesca I. , Oggenfuss Kelly , Ostfeld Richard S.
Published: November 2021

Physical impairments are widely assumed to reduce the viability of individual animals, but their impacts on individuals within natural populations of vertebrates are rarely quantified. By monitoring wild populations of white-footed mice over 26 years, we assessed whether missing or deformed limbs, tail or eyes influenced the survival, body mass, movement and ectoparasite burden of their bearers. Of the 27 244 individuals monitored, 543 (2%) had visible physical impairments. Persistence times (survival) were similar between mice with and without impairments. Mice with eye and tail impairments had 5% and 6% greater mass, respectively, than unimpaired mice. Mice with tail impairments had larger home ranges than did unimpaired mice. Burdens of black-legged ticks (Ixodes scapularis) were higher among mice with tail and limb impairments while burdens of bot fly larvae (Cuterebra) were higher among mice with cataracts compared to mice without impairments. Our findings do not support the presupposition that physical impairments reduce viability in their bearers and are inconsistent with the devaluation of impaired individuals that pervaded early thinking in evolutionary biology.
Insights on the SARS-CoV-2 genome variability: the lesson learned in Brazil and its impacts on the future of pandemics
Authors: Grosche Victória Riquena , Santos Igor Andrade , Ferreira Giulia Magalhães , Dutra João Victor Rodrigues , Costa Larissa Catharina , Nicolau-Junior Nilson , Queiroz Artur Trancoso Lopo , José Diego Pandeló , Jardim Ana Carolina Gomes
Published: November 2021

Since the beginning of the SARS-CoV-2 spread in Brazil, few studies have been published analysing the variability of viral genome. Herein, we described the dynamic of SARS-CoV-2 strains circulating in Brazil from May to September 2020, to better understand viral changes that may affect the ongoing pandemic. Our data demonstrate that some of the mutations identified are currently observed in variants of interest and variants of concern, and emphasize the importance of studying previous periods in order to comprehend the emergence of new variants. From 720 SARS-CoV-2 genome sequences, we found few sites under positive selection pressure, such as the D614G (98.5 %) in the spike, that has replaced the old variant; the V1167F in the spike (41 %), identified in the P.2 variant that emerged from Brazil during the period of analysis; and I292T (39 %) in the N protein. There were a few alterations in the UTRs, which was expected, however, our data suggest that the emergence of new variants was not influenced by mutations in UTR regions, since it maintained its conformational structure in most analysed sequences. In phylogenetic analysis, the spread of SARS-CoV-2 from the large urban centres to the countryside during these months could be explained by the flexibilization of social isolation measures and also could be associated with possible new waves of infection. These results allow a better understanding of SARS-CoV-2 strains that have circulated in Brazil, and thus, with relevant infomation, provide the potential viral changes that may have affected and/or contributed to the current and future scenario of the COVID-19 pandemic.
CompAIRR: ultra-fast comparison of adaptive immune receptor repertoires by exact and approximate sequence matching
Authors: Rognes Torbjørn , Scheffer Lonneke , Greiff Victor , Sandve Geir Kjetil
Published: November 2021

Adaptive immune receptor (AIR) repertoires (AIRRs) record past immune encounters with exquisite specificity. Therefore, identifying identical or similar AIR sequences across individuals is a key step in AIRR analysis for revealing convergent immune response patterns that may be exploited for diagnostics and therapy. Existing methods for quantifying AIRR overlap do not scale with increasing dataset numbers and sizes. To address this limitation, we developed CompAIRR, which enables ultra-fast computation of AIRR overlap, based on either exact or approximate sequence matching. CompAIRR improves computational speed 1000-fold relative to the state of the art and uses only one-third of the memory: on the same machine, the exact pairwise AIRR overlap of 104AIRRs with 105sequences is found in ∼17 minutes, while the fastest alternative tool requires 10 days. CompAIRR has been integrated with the machine learning ecosystem immuneML to speed up various commonly used AIRR-based machine learning applications.

Availability and implementation

CompAIRR code and documentation are available athttps://github.com/uio-bmi/compairr. Docker images are available athttps://hub.docker.com/r/torognes/compairr. The scripts used for benchmarking and creating figures, and all raw data, may be found athttps://github.com/uio-bmi/compairr-benchmarking.
Development of Biologically Interpretable Multimodal Deep Learning Model for Cancer Prognosis Prediction
Authors: Azher Zarif L. , Vaickus Louis J. , Salas Lucas A. , Christensen Brock C. , Levy Joshua J.
Published: November 2021

Robust cancer prognostication can enable more effective patient care and management, which may potentially improve health outcomes. Deep learning has proven to be a powerful tool to extract meaningful information from cancer patient data. In recent years it has displayed promise in quantifying prognostication by predicting patient risk. However, most current deep learning-based cancer prognosis prediction methods use only a single data source and miss out on learning from potentially rich relationships across modalities. Existing multimodal approaches are challenging to interpret in a biological or medical context, limiting real-world clinical integration as a trustworthy prognostic decision aid. Here, we developed a multimodal modeling approach that can integrate information from the central modalities of gene expression, DNA methylation, and histopathological imaging with clinical information for cancer prognosis prediction. Our multimodal modeling approach combines pathway and gene-based sparsely coded layers with patch-based graph convolutional networks to facilitate biological interpretation of the model results. We present a preliminary analysis that compares the potential applicability of combining all modalities to uni- or bi-modal approaches. Leveraging data from four cancer subtypes from the Cancer Genome Atlas, results demonstrate the encouraging performance of our multimodal approach (C-index=0.660 without clinical features; C-index=0.665 with clinical features) across four cancer subtypes versus unimodal approaches and existing state-of-the-art approaches. This work brings insight to the development of interpretable multimodal methods of applying AI to biomedical data and can potentially serve as a foundation for clinical implementations of such software. We plan to follow up this preliminary analysis with an in-depth exploration of factors to improve multimodal modeling approaches on an in-house dataset.
Explaining heterogeneity in medial entorhinal cortex with task-driven neural networks
Authors: Nayebi Aran , Attinger Alexander , Campbell Malcolm G. , Hardcastle Kiah , Low Isabel I.C. , Mallory Caitlin S. , Mel Gabriel C. , Sorscher Ben , Williams Alex H. , Ganguli Surya , Giocomo Lisa M. , Yamins Daniel L.K.
Published: November 2021

Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC — e.g. grid, border, and head-direction cells — whose highly stereotypical response profiles are suggestive of the role they might play in supporting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more “heterogeneous” cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggesting that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles — including those of grid cells themselves — despite not being explicitly trained for this purpose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed in silico experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells are also responsive to non-spatial rewards, we introduce a new MEC model that performs reward-modulated path integration. We find that this unified model matches neural recordings across all variable-reward conditions. Taken together, our results point toward a conceptually principled goal-driven modeling approach for moving future experimental and computational efforts beyond overly-simplistic single-cell stereotypes.
Hybridization and Low Genetic Diversity in the Endangered Alabama Red-Bellied Turtle (Pseudemys alabamensis)
Authors: Moreno Nickolas , Heaton Andrew , Bruening Kaylin , Milligan Emma , Nelson David , Glaberman Scott , Chiari Ylenia
Published: November 2021

Pseudemys alabamensis is one of the most endangered turtle species in the United States due to its small population size and restricted geographic distribution in coastal Alabama and Mississippi. Increased urbanization and climate change impacts in the region further threaten this species. Populations of P. alabamensis are geographically isolated from one another by land and salt water, which could act as barriers to intraspecific gene flow. It is currently unknown how differentiated these isolated populations are from one another or whether they have experienced reductions in population size. Previous work found morphological differences between Alabama and Mississippi populations, suggesting that they may be evolutionarily distinct. Other Pseudemys turtles such as P. concinna and P. floridana occur within the same geographic area as P. alabamensis and are known to hybridize with each other. These more abundant species could further threaten the unique genetic identity of P. alabamensis through introgression. In order to evaluate the endangered status of P. alabamensis and the level of hybridization with other species, we used the mitochondrial (mtDNA) control region and nuclear microsatellite markers to assess genetic variation within and among populations of this species throughout its range and estimate admixture with co-occurring Pseudemys species. Genetic diversity of P. alabamensis was lower than expected at both markers (no variation in mtDNA and excess of homozygosity in microsatellites). We found evidence of genetic differentiation between Alabama and Mississippi populations as well as two populations (Fowl River, Alabama and Biloxi, Mississippi) with low estimated breeding sizes and signs of inbreeding. Finally, we found evidence of admixture of P. alabamensis with P. concinna/P. floridana and Pseudemys peninsularis (a species not native to Alabama or Mississippi). Our results indicate that P. alabamensis is highly endangered throughout its range and threatened by both low population sizes and hybridization. In order to improve the species’ chances of survival, focus should be placed on habitat preservation, maintenance of genetic diversity within both Mississippi and Alabama populations, and regular population monitoring activities such as nest surveillance and estimates of recruitment.
Diversity, function and evolution of marine invertebrate genomes
Authors: Zhang Yaolei , Wang Jiahao , Lv Meiqi , Gao Haoyang , Meng LingFeng , Yunga A , Seim Inge , Zhang He , Liu Shanshan , Zhang Linlin , Liu Xin , Xu Xun , Yang Huanming ,   M10K+ Consortium, Fan Guangyi
Published: November 2021

Invertebrates, animals (metazoans) without backbones, encompass ∼97% of all animal yet remains understudied. They have provided insights into molecular mechanisms underlying fundamentally identical mechanisms in phylogenetically diverse animals, including vertebrates. Marine invertebrates have long fascinated researchers due to their abundance, diversity, adaptations, and impact on ecosystems and human economies. Here, we report a compendium and appraisal of 190 marine invertebrate genomes spanning 21 phyla, 43 classes, 92 orders, and 134 families. We identify a high proportion and long unit size of tandem repeats, likely contributing to reported difficulties in invertebrate genome assembly. A well-supported phylogenetic tree of marine invertebrates from 974 single-copy orthologous genes resolved topological controversies. We show that Ctenophora is at the basal phylum and Porifera is the sister group of Parahoxozoa; that Xenacoelomorpha is within Bilateria and is the sister group to Protostomia, rejecting three out of four hypotheses in the field; and that Bryozoa is at the basal position of Lophotrochozoa, not grouped into Lophophorata. We also present insights into the genetic underpinnings of metazoans from Hox genes, innate immune gene families, and nervous system gene families. Our marine invertebrate genome compendium provides a unified foundation for studies on their evolution and effects on ecological systems and human life.
Dysconnectivity between auditory-cognitive network associated with auditory GABA and glutamate levels in presbycusis patients
Authors: Li Ning , Ma Wen , Ren Fuxin , Li Xiao , Li Fuyan , Zong Wei , Wu Lili , Dai Zongrui , Hui Steve C.N. , Edden Richard A.E. , Li Muwei , Gao Fei
Published: November 2021

Accumulating studies suggest an interaction between presbycusis (PC) and cognitive impairment, which may be explained by the cognitive-ear link to a large extent. However, the neurophysiological mechanisms underlying this link are largely unknown. Here, 51 PC patients and 51 well-matched healthy controls were recruited. We combined resting-state functional MRI and edited magnetic resonance spectroscopy to investigate changes of intra- and inter-network functional connectivity and their relationships with auditory gamma-aminobutyric acid (GABA) and glutamate (Glu) levels and cognitive impairment in PC. Our study confirmed the plastic model of cognitive-ear link at the level of the large-scale brain network, including the dysconnectivity within high-order cognitive networks and between the auditory-cognitive network and overactivation between cognitive networks dependent on hearing loss, which was closely related to the cognitive impairment of PC patients. Moreover, GABA and Glu levels in the central auditory processing were abnormal in patients with PC. Importantly, reduction of GABA-mediated inhibition plays a crucial role in a dysconnectivity between the auditory-cognitive network, which may be neurochemical underpinnings of functional remodeling of cognitive-ear link in PC. Modulation of GABA neurotransmission may enable the development of new therapeutic strategies for the cognitive impairment of PC patients.
Multiple and Dissociable Effects of Sensory History on Working-Memory Performance
Authors: Hajonides Jasper E. , van Ede Freek , Stokes Mark G. , Nobre Anna C. , Myers Nicholas E.
Published: November 2021

Abstract

Behavioural reports of sensory information are biased by stimulus history. The nature and direction of such serial-dependence biases can differ between experimental settings – both attractive and repulsive biases towards previous stimuli have been observed. How and when these biases arise in the human brain remains largely unexplored. They could occur either via a change in sensory processing itself and/or during post-perceptual processes such as maintenance or decision-making. To address this, we analysed behavioural and magnetoencephalographic data from a working-memory task in which participants were sequentially presented with two randomly oriented gratings, one of which was cued for recall at the end of the trial. Behavioural responses showed evidence for two distinct biases: 1) a within-trial repulsive bias away from the previously encoded orientation on the same trial, and 2) a between-trial attractive bias towards the task-relevant orientation on the previous trial. Multivariate classification of stimulus orientation revealed that neural representations during stimulus encoding were biased away from the previous grating orientation, regardless of whether we considered the within- or between-trial prior orientation – despite opposite effects on behaviour. These results suggest that repulsive biases occur at the level of sensory processing and can be overridden at post-perceptual stages to result in attractive biases in behaviour.
Understanding gene regulatory mechanisms based on gene classification
Authors: Tian Hao , He Yueying , Xue Yue , Gao Yi Qin
Published: November 2021

The CpG dinucleotide and its methylation play vital roles in gene regulation as well as 3D genome organization. Previous studies have divided genes into several categories based on the CpG intensity around transcription starting sites (TSS) and found that housekeeping genes tend to possess high CpG density while tissue-specific genes are generally characterized by low CpG density. In this study, we investigated how the CpG density distribution of a gene affects its transcription and regulation pattern. Based on the CpG density distribution around TSS, the human genes are clearly divided into different categories. Not only sequence properties, these different clusters exhibited distinctly different structural features, regulatory mechanisms, and correlation patterns between expression level and CpG/TpG density. These results emphasized that the usage of epigenetic marks in gene regulation is partially rooted in the sequence property of genes, such as their CpG density distribution.
Phylogeography of the desert scorpionMesobuthus mongolicusilluminates a route out of Central Asia and Junggar Basin as a corridor for faunal exchange between Central and East Asia
Authors: Shi Cheng-Min , Zhang Xue-Shu , Liu Lin , Ji Ya-Jie , Zhang De-Xing
Published: November 2021

A comprehensive understanding of the ecological, evolutionary and genetic consequences of climate changes requires integration of information from different geographic regions and ecosystems. However, a clear knowledge gap exists in arid biota of Asian drylands, where climate change and biological evolution demonstrate high regional specificity. We report here our phylogeographic study on the desert scorpionMesobuthus mongolicus, attempting to narrow the gap. Range wide samples for one mitochondrial gene and three nuclear loci were subjected to phylogenetic inferences, molecular dating, Bayesian phylogeographic and demographic reconstructions, and population genetic analyses. Ecological niche modeling was employed to generate models of potential distribution range at present and during the last glacial maximum (LGM). Our results revealed thatM. mongolicusrepresents a single coherent lineage that diverged with its most closely related lineage from Central Asia about 1.36 Ma and underwent radiation ever since. Bayesian phylogeographic reconstruction suggested the ancestral population ofM. mongolicusdispersed gradually eastward through the Junngar Basin to the Gobi region during the late Pleistocene, strengthening the view that the Junggar Basin has constituted an important corridor for faunal exchange between Central Asian and East Asia. We found that the desert scorpion underwent demographic expansion while experiencing range contraction during the LGM. Development of sandy deserts in northwest China incurred by Eurasian aridification might have opened up substantial empty niches that sustained population expansion during the LGM. Our results suggested that organisms’ ecological adaptations have acted as an important determinant for their phylogeographic and demographic responses to past climate changes.
Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination
Authors: Kim Wooseob , Zhou Julian Q. , Sturtz Alexandria J. , Horvath Stephen C. , Schmitz Aaron J. , Lei Tingting , Kalaidina Elizaveta , Thapa Mahima , Alsoussi Wafaa B. , Haile Alem , Klebert Michael K. , Suessen Teresa , Parra-Rodriguez Luis , Mudd Philip A. , Middleton William D. , Teefey Sharlene A. , Pusic Iskra , O’Halloran Jane A. , Presti Rachel M. , Turner Jackson S. , Ellebedy Ali H.
Published: November 2021

Germinal centres (GC) are lymphoid structures where vaccine-responding B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells (BMPCs)1–4. Induction of the latter is a hallmark of durable immunity after vaccination5. SARS-CoV-2 mRNA vaccination induces a robust GC response in humans6–8, but the maturation dynamics of GC B cells and propagation of their progeny throughout the B cell diaspora have not been elucidated. Here we show that anti-SARS-CoV-2 spike (S)-binding GC B cells were detectable in draining lymph nodes for at least six months in 10 out of 15 individuals who had received two doses of BNT162b2, a SARS-CoV-2 mRNA vaccine. Six months after vaccination, circulating S-binding MBCs were detected in all participants (n=42) and S-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of single-cell RNA sequencing of responding blood and lymph node B cells from eight participants and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1540 S-specific B cell clones. SHM accumulated along the B cell differentiation trajectory, with early blood plasmablasts showing the lowest frequencies, followed by MBCs and lymph node plasma cells whose SHM largely overlapped with GC B cells. By three months after vaccination, the frequency of SHM within GC B cells had doubled. Strikingly, S+ BMPCs detected six months after vaccination accumulated the highest level of SHM, corresponding with significantly enhanced anti-S polyclonal antibody avidity in blood at that time point. This study documents the induction of affinity-matured BMPCs after two doses of SARS-CoV-2 mRNA vaccination in humans, providing a foundation for the sustained high efficacy observed with these vaccines.
The NK receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells
Authors: Santara Sumit Sen , Crespo Ângela , Lee Dian-Jang , Hu Jun Jacob , Zhang Ying , Chowdhury Sourav , Meza-Sosa Karla F. , Rowe Marjorie , McClelland Arthur , Wu Hao , Junqueira Caroline , Lieberman Judy
Published: November 2021

Natural killer cells (NK) are a first line of immune defense to eliminate infected, transformed and stressed cells by releasing cytotoxic granules1. NK activation is controlled by the balance of signals transmitted by activating and inhibitory receptors but activating receptor engagement is required to trigger cytotoxicity. The activating receptor NKp46, encoded by the NCR1 gene, is expressed by virtually all NK cells and is the most evolutionarily ancient NK receptor. NKp46 plays a major role in NK recognition of cancer cells, since NKp46 blocking antibodies potently inhibit NK killing of many cancer targets2,3. Although a few viral, fungal and soluble host ligands4 have been identified, the endogenous cell-surface ligand of this important activating NK receptor is unknown. Here we show that NKp46 recognizes and is activated by the P-domain of externalized calreticulin (ecto-CRT). CRT, normally localized to the ER, translocates to the cell surface during ER stress and is a hallmark of chemotherapy-treated dying cancer cells that induce an immune response (immunogenic cell death, ICD)5. NKp46 caps with ecto-CRT in NK immune synapses formed with ecto-CRT-bearing target cells. ER stress, induced by ZIKV infection, ICD-causing chemotherapy drugs and some senescence activators, externalizes CRT and triggers NKp46 signaling. NKp46-mediated killing is inhibited by CRT knockout or knockdown or anti-CRT antibodies and is enhanced by ectopic expression of GPI-anchored CRT. NCR1/Ncr1-deficient human and mouse NK are impaired in killing ZIKV-infected, ER-stressed, and senescent cells and cancer cells that endogenously or ectopically express ecto-CRT. Importantly, NKp46 recognition of ecto-CRT controls the growth of B16 melanoma and RAS-driven lung cancer in mouse models and enhances tumor-infiltrating NK degranulation and cytokine secretion. Thus, ecto-CRT is a danger-associated molecular pattern (DAMP) that is an endogenous NKp46 ligand that promotes innate immune elimination of ER-stressed cells.
Sequence anticipation and spike-time-dependent-plasticity emerge from a predictive learning rule
Authors: Saponati Matteo , Vinck Martin
Published: November 2021

Intelligent behavior depends on the brain’s ability to anticipate future events. However, the learning rules that enable neurons to predict and fire ahead of sensory inputs remain largely unknown. We propose a plasticity rule based on predictive processing, where the neuron learns a low-rank model of the synaptic input dynamics in its membrane potential. Neurons thereby amplify those synapses that maximally predict other synaptic inputs based on their temporal relations, which provide a solution to an optimization problem that can be implemented at the single-neuron level using only local information. Consequently, neurons learn sequences over long timescales and shift their spikes towards the first inputs in a sequence. We show that this mechanism can explain the development of anticipatory signalling and recall in a recurrent network. Furthermore, we demonstrate that the learning rule gives rise to several experimentally observed STDP (spike-timing-dependent plasticity) mechanisms. These findings suggest prediction as a guiding principle to orchestrate learning and synaptic plasticity in single neurons.
Tissue homeostasis in sponges: quantitative analysis of cell proliferation and apoptosis
Authors: Melnikov Nikolai P. , Bolshakov Fyodor V. , Frolova Veronika S. , Skorentseva Ksenia V. , Ereskovsky Alexander V. , Saidova Alina A. , Lavrov Andrey I.
Published: November 2021

Background

Tissues of multicellular animals are maintained due to a tight balance between cell proliferation and programmed cell death. Phylum Porifera is an early branching group of metazoans essential to understanding the key mechanisms of tissue homeostasis. This paper is dedicated to the comparative analysis of proliferation and apoptosis in intact tissues of two sponges belonging to distinct Porifera lineages, Halisarca dujardinii (class Demospongiae) and Leucosolenia variabilis (class Calcarea).

Results

Labeled nucleotides EdU and anti-phosphorylated histone 3 antibodies reveal a considerable number of cycling cells in intact tissues of both species. The main type of cycling cells are choanocytes - flagellated cells of the aquiferous system. The rate of proliferation remains constant in areas containing choanoderm. Cell cycle distribution assessed by the quantitative DNA stain reveals the classic cell cycle distribution curve. During EdU pulse-chase experiments conducted in H. dujardinii, the contribution of the choanocytes to the total amount of EdU-positive cells decreases, while contribution of the mesohyl cells increases. These findings could indicate that the proliferation of the choanocytes is not solely limited to the renewal of the choanoderm, and that choanocytes may participate in the general cell turnover through migration. The number of apoptotic cells in intact tissues of both species is insignificant. In vivo studies in both species with TMRE and CellEvent Caspase-3/7 indicate that apoptosis might be independent of mitochondrial outer membrane permeabilization.

Conclusions

A combination of confocal laser scanning microscopy and flow cytometry provides a quantitative description of cell turnover in intact sponge tissues. Intact tissues of H. dujardinii (Demospongiae) and L. variabilis (Calcarea) are highly proliferative, indicating either high rates of growth or cell turnover. Although the number of apoptotic cells is low, apoptosis could still be involved in the regular cell turnover.
Vertex protein PduN tunes encapsulated pathway performance by dictating bacterial metabolosome morphology
Authors: Mills Carolyn E. , Waltmann Curt , Archer Andre G. , Kennedy Nolan W. , Abrahamson Charlotte H. , Jackson Alexander D. , Roth Eric W. , Shirman Sasha , Jewett Michael C. , Mangan Niall M. , de la Cruz Monica Olvera , Tullman-Ercek Danielle
Published: November 2021

Engineering subcellular organization in microbes shows great promise in addressing bottlenecks in metabolic engineering efforts; however, rules guiding selection of an organization strategy or platform are lacking. Here, we study compartment morphology as a factor in mediating encapsulated pathway performance. Using the 1,2-propanediol utilization microcompartment (Pdu MCP) system from Salmonella enterica serovar Typhimurium LT2, we find that we can shift the morphology of this protein nanoreactor from polyhedral to tubular by removing vertex protein PduN. Analysis of the metabolic function between these Pdu microtubes (MTs) shows that they provide a diffusional barrier capable of shielding the cytosol from a toxic pathway intermediate, similar to native MCPs. However, kinetic modeling suggests that the different surface area to volume ratios of MCP and MT structures alters encapsulated pathway performance. Finally, we report a microscopy-based assay that permits rapid assessment of Pdu MT formation to enable future engineering efforts on these structures.
Hydrogel injection molding to generate complex cell encapsulation geometries
Authors: Emerson Amy E. , McCall Alec B. , Brady Sarah R. , Slaby Emily M. , Weaver Jessica D.
Published: November 2021

Biofabrication methods capable of generating complex, three-dimensional, cell-laden hydrogel geometries are often challenging technologies to implement in the clinic and scaled manufacturing processes. Hydrogel injection molding capitalizes on the reproducibility, efficiency, and scalability of the injection molding process, and we adapt this technique to biofabrication using a library of natural and synthetic hydrogels with varied crosslinking chemistries and kinetics. We use computational modeling to evaluate hydrogel library fluid dynamics within the injection molds in order to predict molding feasibility and cytocompatibility. We evaluate the reproducibility of hydrogel construct molding and extraction and establish criteria for the selection of hydrogels suitable for injection molding. We demonstrate that hydrogel injection molding is capable of generating complex three-dimensional cell-laden construct geometries using diverse hydrogel materials and that this platform is compatible with primary human islet encapsulation. We envision the application of this technique with primary cells via an off-the-shelf clinical kit that can be implemented at the patient bedside by a clinician or integrated with scaled, high-throughput automated cell manufacturing processes to generate encapsulated cell-based therapeutic products.

Graphical Abstract