bluuebunny/crossref_metadata_2025 huggingface dataset:
metaDMG – A Fast and Accurate Ancient DNA Damage Toolkit for Metagenomic Data
Authors: Michelsen Christian , Pedersen Mikkel Winther , Fernandez-Guerra Antonio , Zhao Lei , Petersen Troels C. , Korneliussen Thorfinn Sand
Published: December 2022

MotivationUnder favourable conditions DNA molecules can persist for hundreds of thousands of years. Such genetic remains make up invaluable resources to study past assemblages, populations, and even the evolution of species. However, DNA is subject to degradation, and hence over time decrease to ultra low concentrations which makes it highly prone to contamination by modern sources. Strict precautions are therefore necessary to ensure that DNA from modern sources does not appear in the final data is authenticated as ancient. The most generally accepted and widely applied authenticity for ancient DNA studies is to test for elevated deaminated cytosine residues towards the termini of the molecules: DNA damage. To date, this has primarily been used for single organisms and recently for read assemblies, however, these methods are not applicable for estimating DNA damage for ancient metagenomes with tens and even hundreds of thousands of species.

MethodsWe presentmetaDMG, a novel framework and toolkit that allows for the estimation, quantification and visualization of postmortem damage for single reads, single genomes and even metagenomic environmental DNA by utilizing the taxonomic branching structure. It bypasses any need for initial classification, splitting reads by individual organisms, and realignment. We have implemented a Bayesian approach that combines a modified geometric damage profile with a beta-binomial model to fit the entire model to the individual misincorporations at all taxonomic levels.

ResultsWe evaluated the performance using both simulated and published environmental DNA datasets and compared to existing methods when relevant. We findmetaDMGto be an order of magnitude faster than previous methods and more accurate – even for complex metagenomes. Our simulations show thatmetaDMGcan estimate DNA damage at taxonomic levels down to 100 reads, that the estimated uncertainties decrease with increased number of reads and that the estimates are more significant with increased number of C to T misincorporations.

ConclusionmetaDMGis a state-of-the-art program for aDNA damage estimation and allows for the computation of nucleotide misincorporation, GC-content, and DNA fragmentation for both simple and complex ancient genomic datasets, making it a complete package for ancient DNA damage authentication.
Optimisation of immunocytochemistry methodology for the detection of endogenous eIF2B localised foci
Authors: de Oliveira Madalena I. Ribeiro , Hanson Filipe M. , Hodgson Rachel E. , Cross Alison K , Campbell Susan G. , Allen K. Elizabeth
Published: December 2022

The multisubunit eukaryotic initiation factor 2B (eIF2B), a guanine nucleotide exchange factor (GEF) for eIF2, is an essential regulator of translation initiation. Activation of the cellular integrated stress response (ISR) by factors such as endoplasmic reticulum stress leads to phosphorylation of eIF2α and inhibition of eIF2B GEF activity. Cytoplasmic bodies containing eIF2B subunits, termed eIF2B bodies, have been shown to alter in subunit composition and fluorescence recovery after photobleaching activity in response to the ISR. Analysis of the subunit composition of endogenous eIF2B bodies is dependent on accurate detection of each protein in a cellular context via immunocytochemistry (ICC). We describe bioinformatic techniques to optimize the ICC detection of eIF2B foci in U373 cells. The screening of commercially available primary antibodies against predicted epitopes enhanced measurements of the number, size and fluorescence intensity of eIF2B bodies. A consistent and reproducible ICC analysis of endogenous eIF2B bodies will aid characterisation of eIF2B bodies during the ISR or under disease conditions.

eIF2B is a housekeeping protein and localised eIF2B foci, named eIF2B bodies, can be detected through immunocytochemistry. Here, we discuss the use of immunoinformatics to optimise eIF2B localisation detection.
A liver-specific mitochondrial carrier that controls gluconeogenesis and energy expenditure
Authors: Yook Jin-Seon , Taxin Zachary H. , Yuan Bo , Oikawa Satoshi , Auger Christopher , Mutlu Beste , Puigserver Pere , Hui Sheng , Kajimura Shingo
Published: December 2022

Mitochondria provide essential metabolites and ATP for the regulation of energy homeostasis. For instance, liver mitochondria are a vital source of gluconeogenic precursors under a fasted state. However, the regulatory mechanisms at the level of mitochondrial membrane transport are not fully understood. Here, we report a liver-specific mitochondrial inner-membrane carrier, SLC25A47, which is required for hepatic gluconeogenesis and energy homeostasis. Genome-wide association studies found significant associations betweenSLC25A47and fasting glucose, HbA1c, and cholesterol levels in humans. In mice, we demonstrated that liver-specific deletion ofSlc25a47impaired hepatic gluconeogenesis selectively from lactate, while significantly enhancing whole-body energy expenditure and the hepatic expression of FGF21. These metabolic changes were not a consequence of general liver dysfunction because acute SLC25A47 deletion in adult mice was sufficient to enhance hepatic FGF21 production, pyruvate tolerance, and insulin tolerance independent of liver damage and mitochondrial dysfunction. Mechanistically, SLC25A47 loss leads to impaired hepatic pyruvate flux and malate accumulation in the mitochondria, thereby restricting hepatic gluconeogenesis. Together, the present study identified a crucial node in the mitochondrial inner-membrane that regulates fasting-induced gluconeogenesis and energy homeostasis.

SIGNIFICANCE

Given the impenetrable nature of the mitochondrial inner-membrane, most of the known metabolite carrier proteins, including SLC25A family members, are ubiquitously expressed in mammalian tissues. One exception is SLC25A47 which is selectively expressed in the liver. The present study showed that depletion of SLC25A47 reduced mitochondrial pyruvate flux and hepatic gluconeogenesis under a fasted state, while activating energy expenditure. The present work offers a liver-specific target through which we can restrict hepatic gluconeogenesis, which is often in excess under hyperglycemic and diabetic conditions.
A high-quality reference genome for the fission yeastSchizosaccharomyces osmophilus
Authors: Jia Guo-Song , Zhang Wen-Cai , Liang Yue , Liu Xi-Han , Rhind Nicholas , Pidoux Alison , Brysch-Herzberg Michael , Du Li-Lin
Published: December 2022

Fission yeasts are an ancient group of fungal species that diverged from each other from tens to hundreds of million years ago. Among them is the preeminent model organismSchizosaccharomyces pombe, which has significantly contributed to our understandings of molecular mechanisms underlying fundamental cellular processes. The availability of the genomes ofS. pombeand three other fission yeast speciesS. japonicus,S. octosporus, andS. cryophilushas enabled cross-species comparisons that provide insights into the evolution of genes, pathways, and genomes. Here, we performed genome sequencing on the type strain of the recently identified fission yeast speciesS. osmophilusand obtained a complete mitochondrial genome and a nuclear genome assembly with gaps only at rRNA gene arrays. A total of 5098 protein-coding nuclear genes were annotated and orthologs for more than 95% of them were identified. Genome-based phylogenetic analysis showed thatS. osmophilusis most closely related toS. octosporusand these two species diverged around 16 million years ago. To demonstrate the utility of thisS. osmophilusreference genome, we conducted cross-species comparative analyses of centromeres, telomeres, transposons, the mating-type region, Cbp1 family proteins, and mitochondrial genomes. These analyses revealed conservation of repeat arrangements and sequence motifs in centromere cores, identified telomeric sequences composed of two types of repeats, delineated relationships among Tf1/sushi group retrotransposons, characterized the evolutionary origins and trajectories of Cbp1 family domesticated transposases, and discovered signs of interspecific transfer of two types of mitochondrial selfish elements.
Pediatric critical care capacity in Canada: a national cross-sectional study
Authors: Ganesan Saptharishi Lalgudi , Garros Daniel , Foster Jennifer , Genova Tanya Di , Fontela Patricia S. , Murthy Srinivas ,   the Canadian Critical Care Trials Group (CCCTG)
Published: December 2022

Background

Pediatric intensive care unit (PICU) capacity is a current and future health system challenge in Canada. Despite experiencing two pandemics over the last 15 years and surges in PICU admissions every winter, the bed capacity of Canadian PICUs and their ability to accommodate surges in demand are unknown.

Methods

We conducted an internet-based cross-sectional survey to gather information from Canadian PICUs regarding PICU characteristics, medical staffing, therapies provided, and anticipated challenges related to surge management. The survey was completed by a representative of each PICU and validated by PICU Directors. Quantitative survey results were summarized as counts, proportions, and ratios while qualitative response was analyzed using inductive content analysis.

Results

Representatives from all19 PICUslocated in17 hospitalscompleted the survey and reported having275(217level 3 &58level 2) funded beds with298physical bed spaces. Two PICUs representing47beds (35Level 3 &12Level 2) are specialized cardiac ICUs. Roughly13385, 13419, 11430 and 12315Canadian children were admitted to these PICUs in the years 2018, 2019, 2020 & 2021, respectively. During a surge, PICUs reported being able to add5.9 ± 3.4 (range: 0 – 14)beds per unit and a total of108temporary surge beds. Several barriers for the successful implementation of surge plans were identified.

Interpretation

Canadian pediatric critical care capacity is comparable to other high-income countries, though our ability to respond to a pandemic/epidemic surge with significant pediatric critical illness may be limited.
Characteristics of head and neck alignment and function of deep cervical flexor muscles in patients with nonspecific neck pain
Authors: Kawasaki Tomoko , Ohji Shunsuke , Aizawa Junya , Sakai Tomoko , Hirohata Kenji , Koseki Taiichi , Kuruma Hironobu , Okawa Atsushi , Jinno Tetsuya
Published: December 2022

Objective

To compare forward head posture (FHP) in natural and corrected head postures between patients with nonspecific neck pain (NSNP) and controls, and to clarify the relationship between natural- and corrected-head posture angle differences and deep cervical flexor function.

Design

Survey study

Setting

Patients with NSNP were outpatients at an orthopedic clinic; the controls were community volunteers.

Participants

Thirty-eight patients were divided into the NSNP and control groups (n=19 each), including patients reporting a numerical rating pain score of 3-7 for at least 3 months and those with no neck pain within 12 months previously, respectively.

Interventions

To evaluate FHP, the cranial rotation and vertical angles were measured using lateral photographs of the head and neck. The craniocervical flexion test was used to evaluate deep cervical flexor activation and endurance.

Main outcome measures

We evaluated the head and neck alignment in natural and corrected head postures and the relationship between the degree of change and deep cervical flexor function.

Results

The FHP in the natural head posture did not differ significantly between the groups. For corrected head posture, the FHP was significantly smaller in the NSNP group than in the control group. In the NSNP group, the cranial rotation and vertical angles were significantly different between natural and corrected head postures, and the angle difference between these postures was significantly correlated with deep cervical flexor function.

Conclusions

In patients with NSNP, hypercorrection in the corrected head posture was shown and may be correlated with dysfunction of the deep cervical flexors. Further investigation into the causal relationship between hypercorrection, deep neck flexor dysfunction, and neck pain is required.
Long-term air pollution exposure and markers of cardiometabolic health in the National Longitudinal Study of Adolescent to Adult Health (Add Health) Study
Authors: Bravo Mercedes A. , Fang Fang , Hancock Dana B. , Johnson Eric O. , Harris Kathleen Mullan
Published: December 2022

Background

Air pollution exposure is associated with cardiovascular morbidity and mortality. Although exposure to air pollution early in life may represent a critical window for development of cardiovascular disease risk factors, few studies have examined associations of long-term air pollution exposure with markers of cardiovascular and cardiometabolic health in young adults.

Objectives

By combining health data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) with air pollution data from the Fused Air Quality Surface using Downscaling (FAQSD) archive, we: (1) calculated multi-year estimates of exposure to ozone (O3) and particulate matter with an aerodynamic diameter ≤2.5μm (PM2.5) for Add Health participants; and (2) estimated associations between air pollution exposures and multiple markers of cardiometabolic health.

Methods

Add Health is a nationally representative longitudinal cohort study of over 20,000 adolescents aged 12–19 in the United States (US) in 1994–95 (Wave I). Participants have been followed through adolescence and into adulthood with five in-home interviews. Estimated daily concentrations of O3and PM2.5at census tracts were obtained from the FAQSD archive and used to generate tract-level annual averages of O3and PM2.5concentrations. We estimated associations between average O3and PM2.5exposures from 2002–07 and markers of cardiometabolic health measured at Wave IV (2008–09), including hypertension, hyperlipidemia, body mass index (BMI), diabetes, C-reactive protein, and metabolic syndrome.

Results

The final sample size was 11,259 individual participants. The average age of participants at Wave IV was 28.4 years (range: 24–34 years). In models adjusting for age, race/ethnicity, and sex, long-term O3exposure (2002–07) was associated with elevated odds of hypertension, with an odds ratio (OR) of 1.015 (95% confidence interval [CI]: 1.011, 1.029); obesity (1.022 [1.004, 1.040]); diabetes (1.032 [1.009,1.054]); and metabolic syndrome (1.028 [1.014, 1.041]); PM2.5exposure (2002–07) was associated with elevated odds of hypertension (1.022 [1.001, 1.045]).

Conclusion

Findings suggest that long-term ambient air pollution exposure, particularly O3exposure, is associated with cardiometabolic health in early adulthood.
Linked Patient and Provider Impressions of Outpatient Teleneurology Encounters
Authors: James Justin G. , Park Jane , Oliver Alexandria , Xie Sharon X. , Siderowf Andrew , Spindler Meredith , Wechsler Lawrence , Tropea Thomas F.
Published: December 2022

Background and Objectives

Teleneurology is common in clinical practice partly due to the SARS CoV-2 pandemic. Impressions about teleneurology from patients and providers alike are generally favorable; some of the reported benefits include ease of access to specialized healthcare, savings of time and money, and similar quality of care as an in-person visit. However, comparisons between patient and provider impressions about the same teleneurology encounter have not been described. Here we describe patient impressions about a teleneurology encounter and evaluate concordance with provider impressions about the same encounter.

Methods

Patients and providers at the University of Pennsylvania Hospital Neurology Department were surveyed about their impressions of teleneurology between April 27thand June 16th, 2020. A convenience sample of patients, whose providers completed a questionnaire, were contacted by telephone to solicit their impressions the same encounter. Unique questionnaires for patients and providers focused on similar themes, such as adequacy of technology, assessment of history obtained, and overall quality of the visit. Summaries of patient responses are reported with the raw percent agreement between patients and providers for similar questions.

Results

One hundred thirty-seven patients completed the survey; 64 (47%) were male and 73 were (53%) female. Sixty-six (47%) patients had a primary diagnosis of PD, 42 (30%) a non-PD movement disorder, and 29 (21%) a non-movement disorder neurological disease. One hundred one (76%) were established patient visits and 36 (26%) were new patient visits. Provider responses from 8 different physicians were included. The majority of patients responded that the ease of joining their visit, their comfort engaging with their physicians during their visit, understanding their plan of care after their visit, and the quality of care from their teleneurology visit were satisfactory. Patients and providers agreed about their impressions of the quality of the history obtained (87% agreement), patient-provider relationship (88% agreement), and overall quality of their experience (70% agreement).

Discussion

Patients had favorable impressions about their clinical experience with teleneurology and expressed an interest in incorporating telemedicine visits into their ongoing care. Patients and providers were highly concordant for the history obtained, patient-provider relationship, and overall quality.
COMORBIDITY OF PULMONARY TUBERCULOSIS AND BACTERIAL PNEUMONIA IN PATIENTS WITH LATE STAGES OF HIV-INFECTION WITH IMMUNODEFICIENCY
Authors: Mishina A.V. , Mishin V.Yu. , Shashenkov I. V.
Published: December 2022

Purpose

To study specifics of diagnostics and clinics of comorbidity of pulmonary tuberculosis and bacterial pneumonia in patients with HIV-infection with immunodeficiency.

Materials and methods

Ninety-three first-time diagnosed patients with pulmonary tuberculosis and 4B stage of HIV-infection in the advanced phase in the absence of antiretroviral therapy were examined. The patients were divided into 3 groups. The 1stgroup included 31 patient with pulmonary tuberculosis and pneumonia associated withStreptococcus pneumoniae, the 2ndgroup included 31 patient with pulmonary tuberculosis and pneumonia associated withStaphylococcus aureus. The 3rdgroup included 31 patient without bacterial pneumonia selected by a copy-pair principle. Statistical treatment of the data was performed using Microsoft Office Excel 2019 with calculation of the mean parameter in the group and the standard error of the mean confidence interval (CI).

Results

Comorbidity of pulmonary tuberculosis and pneumonia associated withS. pneumoniaeorS. aureusin patients with 4B stage of HIV-infection with immunodeficiency in the advance phase with absence of antiretroviral treatment is characterized with generalization of tuberculosis and development of opportunistic infections of the lungs with severe clinical picture, high level of drug resistance ofM. tuberculosisand the agents of bacterial pneumonia. At computed tomography of the chest a focal dissemination is revealed in the lungs as well as an intrathoracic lymphadenopathy and changes of the lung pattern, which almost does not differ in patients with bacterial pneumonia.

Conclusion

Clinical signs and X-ray changes in combination of pulmonary tuberculosis and pneumonia associated withS. pneumoniaeorS. aureusand pulmonary tuberculosis with bacterial pneumonia at the late stages of HIV-infection with immunodeficiency have the same type of character that can be diagnosed only with special microbiological viral and molecular genetic studies of abnormal material from the respiratory system and other organs with obligatory determination of drug resistance to the antituberculosis drug products and the antibacterial agents of wide spectrum.
The rate of adaptive molecular evolution in wild and domesticatedSaccharomyces cerevisiaepopulations
Authors: Raas Maximilian W. D. , Dutheil Julien Y.
Published: December 2022

Through its fermentative capacities,Saccharomyces cerevisiaewas central in the development of civilization during the Neolithic period, and the yeast remains of importance in industry and biotechnology giving rise tobona fidedomesticated populations. Here, we conduct a population genomic study of domesticated and wild populations ofS. cerevisiae. Using coalescent analyses, we report that the effective population size of yeast populations decreased since the divergence withS. paradoxus. We fitted models of distribution of fitness effects to infer the rate of adaptive (ωa) and non-adaptive (ωna) non-synonymous substitutions in protein-coding genes. We report an overall limited contribution of positive selection toS. cerevisiaeprotein evolution, albeit with higher rates of adaptive evolution in wild compared to domesticated populations. Our analyses revealed the signature of background selection and possibly Hill-Robertson interference, as recombination was found to be negatively correlated withωnaand positively correlated withωa. However, the effect of recombination onωawas found to be labile, as it is only apparent after removing the impact of codon usage bias on the synonymous site frequency spectrum and disappears if we control for the correlation withωna, suggesting it could be an artefact of the decreasing population size. Furthermore, the rate of adaptive non-synonymous substitutions is significantly correlated with the residue solvent exposure, a relation that cannot be explained by the population’s demography. Together, our results provide a detailed characterization of adaptive mutations in protein-coding genes acrossS. cerevisiaepopulations.
LUC7 proteins define two major classes of 5’ splice sites in animals and plants
Authors: Kenny Connor J. , McGurk Michael P. , Schüler Sandra , Cordero Aidan , Laubinger Sascha , Burge Christopher B.
Published: December 2022

Mutation or deletion of the U1 snRNP-associated factor LUC7L2 is associated with myeloid neoplasms, and knockout of LUC7L2 alters cellular metabolism. Here, we uncover that members of the LUC7 protein family differentially regulate two major classes of 5’ splice sites (5’SS) and broadly regulate mRNA splicing in both human cell lines and leukemias withLUC7L2copy number variation. We describe distinctive 5’SS features of exons impacted by the three human LUC7 paralogs: LUC7L2 and LUC7L enhance splicing of “right-handed” 5’SS with stronger consensus matching on the intron side of the near-invariant /GU, while LUC7L3 enhances splicing of “left-handed” 5’SS with stronger consensus matching upstream of the /GU. We validated our model of sequence-specific 5’SS regulation both by mutating splice sites and swapping domains between human LUC7 proteins. Evolutionary analysis indicates that the LUC7L2/LUC7L3 subfamilies diverged before the divergence of animals and plants. Analysis ofArabidopsis thalianamutants confirmed that plant LUC7 orthologs possess specificity similar to their human counterparts, indicating that 5’SS regulation by LUC7 proteins is deeply conserved.
Deep Learning and Single Cell Phenotyping for Rapid Antimicrobial Susceptibility Testing
Authors: Zagajewski Aleksander , Turner Piers , Feehily Conor , El Sayyed Hafez , Andersson Monique , Barrett Lucinda , Oakley Sarah , Stracy Mathew , Crook Derrick , Nellåker Christoffer , Stoesser Nicole , Kapanidis Achillefs N.
Published: December 2022

The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current gold-standard antimicrobial susceptibility tests (ASTs) are low-throughput and can take up to 48 hours, with implications for patient care. We present advances towards a novel, rapid AST, based on the deep-learning of single-cell specific phenotypes directly associated with antimicrobial susceptibility inEscherichia coli. Our models can reliably (80% single-cell accuracy) classify untreated and treated susceptible cells, across a range of antibiotics and phenotypes - including phenotypes not visually distinct to a trained, human observer. Applying models trained on lab-reference susceptible strains to clinical isolates ofE. colitreated with ciprofloxacin, we demonstrate our models reveal significant (p<0.001) differences between resistant and susceptible populations, around a fixed treatment level. Conversely, deploying on cells treated with a range of ciprofloxacin concentrations, we show single-cell phenotyping has the potential to provide equivalent information to a 24-hour growth AST assay, but in as little as 30 minutes.
Using drivers and transmission pathways to identify SARS-like coronavirus spillover risk hotspots
Authors: Muylaert Renata L. , Wilkinson David A , Kingston Tigga , D’Odorico Paolo , Rulli Maria Cristina , Galli Nikolas , John Reju Sam , Alviola Phillip , Hayman David T. S.
Published: December 2022

The emergence of SARS-like coronaviruses is a multi-stage process from wildlife reservoirs to people. Here we characterize multiple drivers—landscape change, host distribution, and human exposure—associated with the risk of spillover of SARS-like coronaviruses to help inform surveillance and mitigation activities. We consider direct and indirect transmission pathways by modeling four scenarios with livestock and mammalian wildlife as potential and known reservoirs before examining how access to healthcare varies within clusters and scenarios. We found 19 clusters with differing risk factor contributions within a single country (N=9) or transboundary (N=10). High-risk areas were mainly closer (11-20%) rather than far (<1%) from healthcare. Areas far from healthcare reveal healthcare access inequalities, especially Scenario 3, which includes wild mammals as secondary hosts. China (N=2) and Indonesia (N=1) had clusters with the highest risk. Our findings can help stakeholders in land use planning integrating healthcare implementation and One Health actions.
Deep divergence and genomic diversification of gut symbionts of neotropical stingless bees
Authors: Sarton-Lohéac Garance , da Silva Carlos Gustavo Nunes , Mazel Florent , Baud Gilles , de Bakker Vincent , Das Sudip , Chazli Yassine El , Ellegaard Kirsten , Garcia-Garcera Marc , Glover Natasha , Liberti Joanito , Marçal Lorena Nacif , Prasad Aiswarya , Somerville Vincent ,   SAGE class 2019-2020 and 2020-2021, Bonilla-Rosso Germán , Engel Philipp
Published: December 2022

Social bees harbor conserved gut microbiota that may have been acquired in a common ancestor of social bees and subsequently co-diversified with their hosts. However, most of this knowledge is based on studies on the gut microbiota of honey bees and bumble bees. Much less is known about the gut microbiota of the third and most diverse group of social bees, the stingless bees. Specifically, the absence of genomic data from their microbiota presents an important knowledge gap in understanding the evolution and functional diversity of the social bee microbiota. Here we combined community profiling with culturing and genome sequencing of gut bacteria from six neotropical stingless bee species from Brazil. Phylogenomic analyses show that most stingless bee gut isolates form deep-branching sister clades of core members of the honey bee and bumble bee gut microbiota with conserved functional capabilities, confirming the common ancestry and ecology of their microbiota. However, our bacterial phylogenies were not congruent with those of the host indicating that the evolution of the social bee gut microbiota was not driven by strict co-diversification, but included host switches and independent symbiont gain and losses. Finally, as reported for the honey bee and bumble bee microbiota, we find substantial genomic divergence among strains of stingless bee gut bacteria suggesting adaptation to different host species and glycan niches. Our study offers first insights into the genomic diversity of the stingless bee microbiota, and highlights the need for broader samplings to understand the evolution of the social bee gut microbiota.

Importance

Stingless bees are the most diverse group of the corbiculate bees and represent important pollinator species throughout the tropics and subtropics. They harbor specialized microbial communities in their gut that are related to those found in honey bees and bumble bees and that are likely important for bee health. Few bacteria have been cultured from the gut of stingless bees which has prevented characterization of their genomic diversity and functional potential. Here, we established cultures of major community members of the gut microbiota of six stingless bee species and sequenced their genomes. We find that most stingless bee isolates belong to novel bacterial species distantly related to those found in honey bees and bumble bees and encoding similar functional capabilities. Our study offers a new perspective on the evolution of the social bee gut microbiota and presents the basis to characterize the symbiotic relationships between gut bacteria and stingless bees.
Modulation of the E-cadherin in human cells infectedin vitrowithCoxiella burnetii
Authors: Osman Ikram Omar , Mezouar Soraya , Belhaouari-Brahim Djamal , Mege Jean-Louis , Devaux Christian Albert
Published: December 2022

High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as anin vitromodel to investigate the expression and function of E-cad in response to infection byCoxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells withC. burnetiileads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivatedC. burnetii. Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway andCDH1andCTNNB1genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected withC. burnetii. This was particularly evident with the highly virulent strain ofC. burnetii, Guiana. Our data demonstrate that infection of BeWo cells by liveC. burnetiimodulates the E-cad/β-cat signaling pathway.
At Which Low Amplitude Modulated Frequency Do Infants Best Entrain? A Frequency Tagging Study
Authors: Ives James , Labendzki Pierre , Perapoch Amadó Marta , Greenwood Emily , Viswanathan Narain , Northrop Tom , Wass Sam
Published: December 2022

Previous infant entrainment research has shown neural entrainment to a wide range of stimuli and amplitude modulated frequencies. However, it is unknown if infants neurally entrain more strongly to some frequencies more than others, and to which low amplitude modulated frequency infants show the strongest entrainment. The current study seeks to address this by testing the neural entrainment of N=23 4–6-month-old infants and N=22 control group adult caregivers while they listened to a range of sinusoidally amplitude modulated beep stimuli at rest (no sound), 2, 4, 6, 8, 10 and 12 Hz. Analysis examined differences across power and phase, regions of interest predetermined by previous literature and by segmented time windows. Results showed that the strongest entrainment was at 2Hz for both adult and infant participants; that there was no significant difference in power and phase, entrainment was occipital temporal and slightly left fronto-central in adults and right fronto-central and left occipito-temporal in infants, leading to some regions of interest used in previous studies being significant in infants and all regions of interest being significant in adults. Segmenting by time window did not show any significant increase or decrease in entrainment over time, but longer time windows showed a stronger entrainment response. In conclusion, it is important to choose appropriate stimulation frequencies when investigating entrainment between stimulation frequencies or across ages; whole head recording is recommended to see the full extent of activation; there is no preference on power vs phase analyses; and longer recordings show stronger effects.

Author Contribution Statement

Ives, J., conceptualisation, data collection and curation, formal analysis, methodology, writing – original draft; Labendzki, P., data collection and curation, formal analysis, writing – review & editing; Perapoch Amadó, M., data collection and curation, writing – review & editing; Greenwood, E., data collection and curation, participant recruitment, writing – review & editing; Viswanathan, N., data collection and curation, writing – review & editing; Northrop, T., data collection and curation, participant recruitment, writing – review & editing; Wass, S., conceptualisation, funding acquisition, methodology, project administration, supervision, writing – review & editing.

Highlights

2Hz amplitude modulation stimulation showed the strongest neural entrainment

We discuss power vs phase analyses of infant and adult frequency tagging responses

We illustrate topographic differences in adult and infant neural responses
Adult born hippocampal granule cells promote pattern separation by bidirectionally modulating the remapping of place and cue cells
Authors: Tuncdemir Sebnem N. , Grosmark Andres D. , Chung Hannah , Luna Victor M. , Lacefield Clay O. , Losonczy Attila , Hen Rene
Published: December 2022

The hippocampal dentate gyrus (DG) exhibits a unique form of neural plasticity that results from continuous integration of adult born neurons, referred to as ‘adult neurogenesis’. Recent studies have proposed that adult neurogenesis promotes the ability to encode new memories without interference from previously stored memories that share similar features, through a neural computation known as pattern separation. However, due to lack ofin vivophysiological evidence, the manner in which adult neurogenesis contributes to pattern separation remains unknown. Here, we investigate the contribution of functionally integrated yet immature adult born granule cells (iGCs) to DG computations by examining how chronic ablation or acute chemogenetic silencing of iGCs affects the activity of mature granule cells (mGCs) usingin vivo2-photon Ca2+imaging. In both cases we observed altered remapping of mGCs but in opposite directions depending on their tuning selectivity. Rather than broadly modulating the activity of all mGCs, iGCs promote the remapping of place cells but limit the remapping of mGCs representing sensory cues (cue cells). We propose that these properties of iGCs explain their role in pattern separation because they promote the formation of non-overlapping representations for identical sensory cues encountered in different locations. Conversely, the absence of iGCs shifts the DG network to a state dominated by sensory cue information, a situation that is consistent with the overgeneralization often observed in anxiety disorders such as PTSD.
Inhibitory gating of thalamocortical inputs onto rat gustatory insular cortex
Authors: Haley Melissa S. , Fontanini Alfredo , Maffei Arianna
Published: December 2022

In the rat primary gustatory cortex (GC), a subregion of the larger insular cortex, neurons display time-varying neural responses to gustatory stimuli. GC taste responses are dramatically reduced following inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc). Pharmacological inactivation of VPMpc also has a profound effect on GC spontaneous activity. This indicates that the projection from VPMpc plays a crucial role in GC taste processing as well as in the control of its state. How VPMpc afferents engage GC circuits and drive neuronal ensembles to effectively code tastant identity, as well as modulate the overall state of the GC network, remains unclear. To investigate the synaptic properties and organization of VPMpc afferents in GC, we employed a circuit-breaking optogenetic approach, stimulating VPMpc terminal fields while performing whole-cell patch clamp recordings from GC neurons in rat acute slices. Informed by previous studies of thalamocortical inputs to other sensory cortices, we hypothesized that VPMpc-GC synapses have laminar- and cell-specific properties that gate sensory input, conferring computationally flexibility to how taste information is processed in GC. We found that VPMpc-GC synapses are strongly gated by the activity regime of VPMpc afferents, as well as by feedforward and feedback inhibition onto VPMpc terminals. These results provide novel insight into the circuit underpinning of GC responsiveness to incoming thalamocortical activity.

SIGNIFICANCE STATEMENT

We report that the input from the primary taste thalamus to the primary gustatory cortex (GC) shows distinct properties compared to primary thalamocortical synapses onto other sensory areas. VPMpc afferents in GC make synapses with excitatory neurons distributed across all cortical layers and display frequency-dependent short-term plasticity to repetitive stimulation, thus they do not fit the classic distinction between drivers and modulators typical of other sensory thalamocortical circuits. Feedforward inhibition gates thalamocortical activation and provides local corticothalamic feedback via presynaptic ionotropic and metabotropic GABA receptors. The connectivity and inhibitory control of thalamocortical synapses support the time-varying response dynamics to taste stimuli observed in GC neuronsin vivo.
Spontaneous activation of cortical somatosensory networks depresses their excitability in preterm human neonates
Authors: Whitehead Kimberley , Rupawala Mohammed , Laudiano-Dray Maria Pureza , Meek Judith , Olhede Sofia , Fabrizi Lorenzo
Published: December 2022

Introduction

The activity of the developing cortex is characteristically discontinuous where sudden high amplitude bursts interrupt periods of quiescent background. While the functional importance of this activity is clear, its aetiology is not known. Here, we hypothesise that this alternating pattern arises because of “refractoriness” of cortical networks following spontaneous activation.

Methods

To test this hypothesis, we assessed whether spontaneous activity in sensory networks depressed their excitability by measuring the impact of ongoing activity on the response to an external sensory stimulus. We recorded cortical activity before and after mechanical tactile stimulation of hands and feet in 35 preterm infants of median 32 weeks post-menstrual age.

Results

Mechanical stimulation evoked wideband energy increases with two distinct peaks within the delta and alpha-beta band. The delta activity engaged extended cortical areas, while the faster activity engaged local somatotopically specific areas. By then characterising the spectro-spatial properties of the spontaneous activity preceding stimulation, we showed that baseline energy with a distribution and spectral profile similar to that of somatosensory-evoked activity dampened the energy changes elicited by touching the body.

Discussion

Sensory-evoked activity in preterm human neonates likely represents the coordinated activation of extended (tangential) and local (e.g. columnar) cortical aggregates. The occurrence of spontaneous cortical events in the same cortical regions depresses their excitability preventing their immediate re-engagement. This “refractoriness” offers the first etiological explanation to the cyclical burst-quiescence pattern typical of preterm cortical activity.
Local angiogenic interplay of Vegfc/d and Vegfa drives brain region-specific development of fenestrated capillaries
Authors: Parab Sweta , Card Olivia A. , Chen Qiyu , Buck Luke D. , Quick Rachael E. , Horrigan William F. , Levkowitz Gil , Vanhollebeke Benoit , Matsuoka Ryota L.
Published: December 2022

Fenestrated and blood-brain barrier (BBB)-forming endothelial cells constitute major brain capillaries, and this vascular heterogeneity is crucial for region-specific neural function and brain homeostasis. How these capillary types emerge in a brain region-specific manner and subsequently establish intrabrain vascular heterogeneity remains unclear. Here, we show a core angiogenic mechanism critical for fenestrated brain capillary development via a comparative analysis of the zebrafish choroid plexuses (CPs) and circumventricular organs (CVOs), demonstrating capillary-type-selective vascularization mechanisms. We found that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely-impaired BBB angiogenesis without any apparent defect in fenestrated capillary formation in the CPs and CVOs. Conversely, simultaneous genetic loss of various Vegf combinations revealed remarkable heterogeneity of endothelial requirements for Vegfs-dependent angiogenesis within and across these organs, identifying unexpected interplay of Vegfc/d and Vegfa in fenestrated brain capillary formation. Expression analysis and paracrine activity-deficientvegfcmutant characterization suggest that endothelial cells and non-neuronal specialized cell types present in the CPs and CVOs are major sources of Vegfs responsible for regionally-restricted angiogenic interplay. Thus, local presentations and interplay of Vegfc/d and Vegfa control brain region-specific emergence of fenestrated capillaries, providing insight into fenestrated capillary formation in other organs and also how intra-organ vascular heterogeneity arises.
Pain and cognitive performance in adults with multiple sclerosis: A systematic review
Authors: Brown Fraser S , Glasmacher Stella A , Taylor Daniel , Jenkins Ruth , Chandran Siddharthan , Gillespie David , Foley Peter
Published: December 2022

Introduction

Pain and cognitive dysfunction are separately known to be important manifestations of multiple sclerosis (MS). Although pain is a complex subjective phenomenon with affective and cognitive aspects, it is not known if people with MS reporting pain are at greater risk of reduced performance in objective tests of cognition. The presence or direction of any association remains to be clarified, as do the roles of confounders such as fatigue, medication and mood.

Methods

We conducted a systematic review of studies examining the relationship between pain and objectively measured cognition in adults with confirmed MS, according to a pre-registered protocol (PROSPERO 42020171469). We carried out searches in MEDLINE, Embase and PsychInfo. We evaluated the role of potential confounders (medication, depression, anxiety, fatigue and sleep) and described findings by eight pre-specified cognitive domains.

Results

11 studies (n=3714, range 16 to 1890 participants per study) were included in the review. Four studies included longitudinal data. Nine studies identified a relationship between pain and objectively measured cognitive performance. In seven of these studies, higher pain scores were associated with poorer cognitive performance. However, no evidence was available for some cognitive domains. Heterogeneous study methodology precluded meta-analysis. Studies infrequently controlled for the specified confounders. Most studies were judged to be at risk of bias.

Discussion

Several studies, but not all, identified a negative relationship between pain severity and objectively measured cognitive performance. Our ability to further characterise this relationship is limited by study design and lack of evidence in many cognitive domains. Future studies should better establish this relationship and delineate the neurological substrate underpinning it.
TMPRSS2 is essential for SARS-CoV-2 Beta and Omicron infection
Authors: Metzdorf Kristin , Jacobsen Henning , Greweling-Pils Marina C. , Hoffmann Markus , Lüddecke Tatjana , Miller Felicitas , Melcher Lars , Kempf Amy M. , Nehlmeier Inga , Bruder Dunja , Widera Marek , Ciesek Sandra , Pöhlmann Stefan , Čičin-Šain Luka
Published: December 2022

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts whether TMPRSS2 inhibitors would be suitable for treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to spread of SARS-CoV-2 in the infected host is largely unclear. Here, we show that loss of TMPRSS2 strongly reduced the replication of the Beta variant in nose, trachea and lung of C57BL mice and protected the animals from weight loss and disease. Infection of mice with the Omicron variant did not cause disease, as expected, but again TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify a key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection and highlight TMPRSS2 as an attractive target for antiviral intervention.
New measurement system based on small-angle neutron scattering for structural analysis of light-responsive materials
Authors: Iwase Hiroki , Akamatsu Masaaki , Inamura Yasuhiro , Sakaguchi Yoshifumi , Morikawa Toshiaki , Kasai Satoshi , Oh-uchi Keiichi , Kobayashi Kazuki , Sakai Hideki
Published: December 2022

With the increasing importance of light-responsive materials, it is vital to analyze the relationship between function and structural changes induced by light irradiation. Small-angle scattering (SAS) is effective for such structural analysis. However, quantitatively capturing local molecular structure formation and molecular reactions at a scale of less than 1 nm via SAS is difficult. In this study, to analyze the structure of non-equilibrium phenomena in light-responsive materials, a new sample environment has been developed for a time-of-flight small- and wide-angle neutron scattering instrument (TAIKAN), comprising a UV–Vis irradiation system, UV–Vis absorption measurement equipment and photodetector. Simultaneous measurement of small-angle neutron scattering and UV–Vis absorption was achieved. This system was used to demonstrate the in situ observation of UV–Vis irradiation-induced structural change of micelles formed by 4-butylazobenzene-4′-(oxyethyl)trimethylammonium bromide, which is a light-responsive surfactant, in an aqueous solution. The results showed that the present measuring system provides direct information on the interplay between changes in micelle structure and changes in molecular configuration.
Synthesis, crystal structure and thermal properties of bis(acetonitrile-κN)bis(3-bromopyridine-κN)bis(thiocyanato-κN)cobalt(II)
Authors: Krebs Christoph , Jess Inke , Näther Christian
Published: December 2022

Single crystals of the title compound, [Co(NCS)2(C5H4BrN)2(C2H3N)2], were obtained by the reaction of Co(NCS)2 with 3-bromopyridine in acetonitrile. The CoII cations lie on crystallographic inversion centers and are coordinated by two N-bonded thiocyanate anions, two 3-bromopyridine and two acetonitrile ligands thereby forming slightly distorted CoN6 octahedra. In the crystal, these complexes are linked by C—H...S and C—H...N hydrogen bonds into a three-dimensional network. In the direction of the crystallographic b-axis, the complexes are arranged into columns with neighboring 3-bromopyridine ligands stacked onto each other, indicating π–π interactions. The CN stretching vibration of the thiocyanate anions is observed at 2066 cm−1, in agreement with the presence of only N-bonded anionic ligands. TG-DTA measurements reveal that in the first mass loss the acetonitrile ligands are removed and that in the second step, half of a 3-bromopyridine ligand is lost, leading to the formation of a polymeric compound with the composition [(Co(NCS)2)2(C5H4BrN)3]
n
already reported in the literature.