bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term clade-wide shifts in trilobite segment number and allocation during the Palaeozoic
Authors: Hopkins Melanie J. , To Rebecca
Published: December 2022

Arthropods are characterized by having an exoskeleton, paired jointed appendages and segmented body. The number and shape of those segments vary dramatically and unravelling the evolution of segmentation is fundamental to our understanding of arthropod diversification. Because trilobites added segments to the body post-hatching which were expressed and preserved in biomineralized exoskeletal sclerites, their fossil record provides an excellent system for understanding the early evolution of segmentation in arthropods. Over the last 200 years, palaeontologists have hypothesized trends in segment number and allocation in the trilobite body, but they have never been rigorously tested. We tabulated the number of segments in the post-cephalic body for over 1500 species, selected to maximize taxonomic, geographical and temporal representation. Analysis reveals long-term shifts in segment number and allocation over the 250-million-year evolutionary history of the clade. For most of the Palaeozoic, the median number of segments in the body did not change. Instead, the total range decreased over time and there was long-term increase in the proportion of segments allocated to the fused terminal sclerite relative to the articulated thoracic region. There was also increased conservation of thoracic segment number within families. Neither taxonomic turnover nor trends in functionally relevant defensive behaviour sufficiently explain these patterns.
Lower respiratory tract microbiome composition and community interactions in smokers
Authors: Campos Michael , Cickovski Trevor , Fernandez Mitch , Jaric Melita , Wanner Adam , Holt Gregory , Donna Elio , Mendes Eliana , Silva-Herzog Eugenia , Schneper Lisa , Segal Jonathan , Amador David Moraga , Riveros Juan Daniel , Aguiar-Pulido Vanessa , Banerjee Santanu , Salathe Matthias , Mathee Kalai , Narasimhan Giri
Published: December 2022

The lung microbiome impacts lung function, making any smoking-induced changes in the lung microbiome potentially significant. The complex co-occurrence and co-avoidance patterns between the bacterial taxa in the LRT microbiome were explored for a cohort of active (AS), former (FS), and never (NS) smokers. Bronchoalveolar lavages (BAL) were collected from 55 volunteer subjects (nine NS, 24 FS, and 22 AS). The LRT microbiome composition was assessed using 16S rRNA amplicon sequencing. Identification of differentially abundant taxa, co-occurrence patterns, discriminant analysis, and biomarker inferences were performed. The data show that smoking results in a loss in the diversity of the lower respiratory tract (LRT) microbiome, change in the co-occurrence patterns, and a weakening of the tight community structure present in healthy microbiomes. The increased abundance of Ralstonia genus in the lung microbiomes of both former and active smokers is significant.
Partial least square discriminant and DESeq2 analyses suggested a compositional difference between the cohorts in the LRT microbiome. The groups were sufficiently distinct from each other, suggesting that cessation of smoking may not be sufficient for      the lung microbiota to return to a composition similar to that of never smokers. The LEfSe analyses identified several bacterial taxa as potential biomarkers of smoking status. Network-based clustering analysis highlighted different co-occurring and co-avoiding microbial taxa in the three groups. The analysis found a cluster of bacterial taxa that co-occur in smokers and non-smokers alike. The clusters exhibited tighter and more significant associations in NS compared to FS and AS. Higher degree of rivalry between clusters was observed in the AS.  The groups were sufficiently distinct from each other, suggesting that cessation of smoking may not be sufficient for the lung microbiota to return to a composition similar to that of never smokers.
Challenges and opportunities in the development of novel antimicrobial therapeutics for cystic fibrosis
Authors: Barton Thomas E. , Frost Frederick , Fothergill Joanne L. , Neill Daniel R.
Published: December 2022

Chronic respiratory infection is the primary driver of mortality in individuals with cystic fibrosis (CF). Existing drug screening models utilised in preclinical antimicrobial development are unable to mimic the complex CF respiratory environment. Consequently, antimicrobials showing promising activity in preclinical models often fail to translate through to clinical efficacy in people with CF. Model systems used in CF anti-infective drug discovery and development range from antimicrobial susceptibility testing in nutrient broth, through to 2D and 3D in vitro tissue culture systems and in vivo models. No single model fully recapitulates every key aspect of the CF lung. To improve the outcomes of people with CF (PwCF) it is necessary to develop a set of preclinical models that collectively recapitulate the CF respiratory environment to a high degree of accuracy. Models must be validated for their ability to mimic aspects of the CF lung and associated lung infection, through evaluation of biomarkers that can also be assessed following treatment in the clinic. This will give preclinical models greater predictive power for identification of antimicrobials with clinical efficacy. The landscape of CF is changing, with the advent of modulator therapies that correct the function of the CFTR protein, while antivirulence drugs and phage therapy are emerging alternative treatments to chronic infection. This review discusses the challenges faced in current antimicrobial development pipelines, including the advantages and disadvantages of current preclinical models and the impact of emerging treatments.
An oral vaccine for SARS-CoV-2 RBD mRNA-bovine milk-derived exosomes induces a neutralizing antibody responsein vivo
Authors: Zhang Quan , Wang Miao , Han Chunle , Wen Zhijun , Meng Xiaozhu , Qi Dongli , Wang Na , Du Huanqing , Wang Jianhong , Lu Lu , Ge Xiaohu
Published: December 2022

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has presented numerous challenges to global health. The vaccines, including lipid-based nanoparticle mRNA, inactivated virus and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and are immensely helpful against the epidemic. Here, we first present an oral mRNA vaccine based on bovine milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor binding domain (RBD) as an immunogen. The results indicated that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptide in 293 cellsin vitroand stimulated neutralizing antibodies against RBD in mice. These results indicated that bovine milk-derived exosome-based mRNA vaccine could serve as a new strategy for preventing SARS-CoV-2 infection. Meanwhile, it also can work as a new oral delivery system for mRNA.

One Sentence Summary

Oral SARS-CoV-2 mRNA vaccine based on bovine milk-derived exosomes can stimulate neutralizing antibodies in mice.
Centromere Pairing in Prophase Allows Partner Chromosomes to Orient on the Meiosis I Spindle
Authors: Evatt Jared M. , Chuong Hoa H. , Meyer Régis E. , Dawson Dean S.
Published: December 2022

Proper chromosome segregation in meiosis I relies on the formation of connections between homologous chromosomes. Crossovers between homologs provide a connection that allows them to attach correctly to the meiosis I spindle. Tension is transmitted across the crossover when the partners attach to microtubules from opposing poles of the spindle. Tension stabilizes microtubule attachments that will pull the partners towards opposite poles at anaphase1,2. Paradoxically, in many organisms, non-crossover partners segregate correctly3. The mechanism by which non-crossover partners become bi-oriented on the meiotic spindle is unknown. Both crossover and noncrossover partners pair their centromeres in early in meiosis (prophase). In budding yeast, centromere pairing, is correlated with subsequent correct segregation of the partners4,5. The mechanism by which centromere pairing, in prophase, promotes later correct attachment of the partners to the metaphase spindle is unknown. We used live cell imaging to track the bi-orientation process of non-crossover chromosomes. We find that centromere pairing allows the establishment of connections between the partners that allows their later interdependent attachment to the meiotic spindle using tensionsensing bi-orientation machinery. Because all chromosome pairs experience centromere pairing, our findings suggest that crossover chromosomes also utilize this mechanism to achieve maximal segregation fidelity.
A hierarchical model for external electrical control of an insect, accounting for inter-individual variation of muscle force properties
Authors: Owaki Dai , Dürr Volker , Schmitz Josef
Published: December 2022

Cyborg control of insect movement is promising for developing miniature, high-mobility, and efficient biohybrid robots. However, considering the inter-individual variation of the insect neuromuscular apparatus and its neural control is challenging. We propose a hierarchical model including inter-individual variation of muscle properties of three leg muscles involved in propulsion (retractor coxae), joint stiffness (pro- and retractor coxae), and stance-swing transition (protractor coxae and levator trochanteris) in the stick insectCarausius morosus. To estimate mechanical effects induced by external muscle stimulation, the model is based on the systematic evaluation of joint torques as functions of electrical stimulation parameters. A nearly linear relationship between the stimulus burst duration and generated torque was observed. This stimulus-torque characteristic holds for burst durations of up to 500 ms, corresponding to the stance and swing phase durations of medium to fast walking stick insects. Hierarchical Bayesian modeling revealed that linearity of the stimulus-torque characteristic was invariant, with individually varying slopes. Individual prediction of joint torques provides significant benefits for precise cyborg control.
Rapid recall andde novoT cell responses during SARS-CoV-2 breakthrough infection
Authors: Koutsakos Marios , Reynaldi Arnold , Lee Wen Shi , Nguyen Julie , Amarasena Thakshila , Taiaroa George , Kinsella Paul , Liew Kwee Chin , Tran Thomas , Kent Helen E , Tan Hyon-Xhi , Rowntree Louise C , Nguyen Thi H O , Thomas Paul G , Kedzierska Katherine , Petersen Jan , Rossjohn Jamie , Williamson Deborah A , Khoury David , Davenport Miles P , Kent Stephen J , Wheatley Adam K , Juno Jennifer A
Published: December 2022

While the protective role of neutralising antibodies against COVID-19 is well-established, questions remain about the relative importance of cellular immunity. Using 6 pMHC-multimers in a cohort with early and frequent sampling we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection. Recall of spike-specific CD4+T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post-symptom onset. Similarly, spike-specific CD8+T cells were rapidly activated but showed variable levels of expansion. Strikingly, high levels of SARS-CoV-2-specific CD8+T cell activation at baseline and peak were strongly correlated with reduced peak SARS-CoV-2 RNA levels in nasal swabs and accelerated clearance of virus. Our study demonstrates rapid and extensive recall of memory T cell populations occurs early after breakthrough infection and suggests that CD8+T cells contribute to the control of viral replication in breakthrough SARS-CoV-2 infections.
Pharmacological elevation of cellular dihydrosphingomyelin provides a novel antiviral strategy against West Nile virus infection
Authors: Jiménez de Oya Nereida , San-Félix Ana , Casasampere Mireia , Blázquez Ana-Belén , Mingo-Casas Patricia , Escribano-Romero Estela , Calvo-Pinilla Eva , Poderoso Teresa , Casas Josefina , Saiz Juan-Carlos , Pérez-Pérez María-Jesús , Martín-Acebes Miguel A.
Published: December 2022

Flavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our own collection of polyphenols against West Nile virus, a representative medically relevant flavivirus, led to the identification ofN,N′-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (EC50of 2.2 and 0.24 μM, respectively in Vero cells; EC50of 2.2 and 1.9 μM, respectively in SH-SY5Y cells). These polyphenols also inhibited the multiplication of other flaviviruses, namely Usutu, dengue, and Zika viruses, exhibiting lower antiviral or negligible antiviral activity against other RNA viruses. The mechanism underlying their antiviral activity against WNV involved the alteration of sphingolipid metabolism. These compounds inhibited ceramide desaturase (Des1) promoting the accumulation of dihydrosphingomyelin (dhSM), a minor component of cellular sphingolipids with important roles on membrane properties. Addition of exogenous dhSM, or Des1 blockage by using the reference inhibitor GT-11, confirmed the involvement of this pathway in WNV infection. These results unveil the potential of novel antiviral strategies based on the modulation of the cellular levels of dhSM and Des1 activity for the control of flavivirus infection.
Self-reported and measured anthropometric variables in association with cardiometabolic markers: a Danish cohort study
Authors: Zhang Jie , Olsen Anja , Halkjær Jytte , Petersen Kristina Elin Nielsen , Tjønneland Anne , Overvad Kim , Dahm Christina C
Published: December 2022

Self-reported measures of height and weight are widely used in epidemiological studies. However, misreporting may bias estimates of associations between anthropometry and health outcomes. Further, few validation studies have compared self-reported and measured waist circumference (WC). This study aimed to quantify the agreement between self-reported and measured height, weight, body mass index (BMI), WC, and waist-to-height ratio (WHtR), and to investigate associations of these anthropometric measures with cardiometabolic biomarkers.

Self-reported and measured anthropometric variables, as well as cardiometabolic biomarkers, were obtained from participants aged above 18 years at recruitment into the Diet, Cancer, and Health-Next Generation Cohort in 2015-19 (N=39,514). Pearson correlations (r) and Lin’s concordance correlations were applied to evaluate misreporting. Misreporting by age, sex and smoking status was investigated in linear regression models. Multivariable regression models and Receiver Operating Characteristic analyses assessed associations of self-reported and measured anthropometry with cardiometabolic biomarkers. Self-reported height was overreported by 1.07 cm, and weight was underreported by 0.32 kg on average. Self-reported BMI and WC were 0.42 kg/m2and 0.2 cm lower than measured, respectively. Self-reported and measured height, weight, BMI, WC and WtHR were strongly correlated (r=0.98, 0.99, 0.98, 0.88, 0.86, respectively). Age, sex, smoking, and BMI contributed to misreporting of all anthropometric measures. Associations between self-reported or measured anthropometric measures and cardiometabolic biomarkers were similar in direction and strength. Concordance between self-reported and measured anthropometric measures, including WC, was very high. Self-reported anthropometric measures were reliable when estimating associations with cardiometabolic biomarkers.
Target height influences shoulder and elbow non-use after stroke during reaching with the hand : A brief communication
Authors: Faity Germain , Mottet Denis , Froger Jérôme
Published: December 2022

Background

During hand reaching movements in people with stroke, the coordination of trunk, shoulder, and elbow muscles changes as a function of target height. However, it is not known whether target height also influences non-use, defined as the difference between two coordinations aiming at the same target.

Methods

Twenty-two individuals with stroke (> 1 month) completed the Proximal Arm Non-Use (PANU) test in two conditions: high target (80 cm) and low target (67 cm). Elbow, shoulder, and trunk use was recorded using motion capture.

Results

Trunk compensation and non-use of the shoulder and elbow joints were found to depend on target height.

Conclusions

Because trunk bending forward goes against the need to elevate the hand, a sufficiently low target is necessary to unmask the presence of shoulder-elbow non-use. We provide novel recommendations for assessing compensations and non-use during hand reaching. Clinical Trial:NCT04747587.
Adherence to Pre-exposure Prophylaxis intervention by transgender women: A systematic review
Authors: Moncayo-Quevedo Jorge Eduardo , Mar Pérez-Arizabaleta María Del , María Villegas-Trujillo Lina , Rodríguez-Ortiz Alejandra
Published: December 2022

Background

The prevalence of HIV is higher in the transgender population. Recently, the preexposure prophylaxis (PrEP) intervention has been proven successful in reducing HIV acquisition in trials among men who have sex with men (MSM), and heterosexual couples. This research aims to investigate the adherence to PrEP by HIV-negative transgender women (TW).

Methods

Were followed the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Statement. Research in WoS, Ovid, Scopus, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases for studies that involved HIV-negative TW population and focused on their adherence to PrEP intervention and condom use after the treatment.

Results

11 studies were included. TW sample sizes were low in comparison to the total sample, which often included men who have sex with men (MSM) population. The participation and adherence to the intervention was low compared to MSM, and it was measured mainly by self-report (72.7%) or by Tenofovir-diphosphate (TFV-DP)/ Emtricitabine triphosphate (FTC-TP) dried blood spot (DBS) (45.5%).

Conclusions

It is important to increase awareness and explain the effect of PrEP on feminizing hormone therapy at the beginning of the trials. Nevertheless, the low adherence may be affected by the interaction between drugs and the barriers faced to use the health services.
Nucleosome repositioning in chronic lymphocytic leukaemia
Authors: Piroeva Kristan V. , McDonald Charlotte , Xanthopoulos Charalampos , Fox Chelsea , Clarkson Christopher T. , Mallm Jan-Philipp , Vainshtein Yevhen , Ruje Luminita , Klett Lara C. , Stilgenbauer Stephan , Mertens Daniel , Kostareli Efterpi , Rippe Karsten , Teif Vladimir B.
Published: December 2022

The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we performed a systematic comparison of high-resolution nucleosome maps in peripheral-blood B-cells from patients with chronic lymphocytic leukaemia (CLL) and healthy individuals at single base pair resolution. Our investigation uncovered significant changes of both nucleosome positioning and packing in CLL. Globally, the spacing between nucleosomes (the nucleosome repeat length, NRL) was shortened in CLL. This effect was stronger in the more aggressive IGHV-unmutated than IGHV-mutated CLL subtype. Changes in nucleosome occupancy at specific sites were linked to active chromatin remodelling and reduced DNA methylation. Nucleosomes lost or gained in CLL in comparison with non-malignant B-cells marked differential binding of 3D chromatin organisers such as CTCF as well as immune response-related transcription factors, allowing delineating epigenetic mechanisms affected in CLL. Furthermore, patients could be better assigned to CLL subtypes according to nucleosome occupancy at cancer-specific sites than based on DNA methylation or gene expression. Thus, nucleosome positioning constitutes a novel readout to dissect molecular mechanisms of disease progression and to stratify patients. Furthermore, we anticipate that the global nucleosome positioning changes detected in our study, like the reduced NRL, can be exploited for liquid biopsy applications based on cell-free DNA to monitor disease progression.
Metabolism is correlative not causative for age-related auditory decline in an insect model
Authors: Austin Thomas T , Thomas Christian , Clifton Lewis , Blockley Alix , Warren Ben
Published: December 2022

Aging is due to a complex decline of multiple biological processes. Some of the causes include oxidative damage, mitochondrial and proteostatic dysfunction, and DNA damage. The result is that as biological systems age their performance deteriorates. This age-related decline is well quantified, and experienced, for human hearing and is presumed to be due to a decrease in the ear’s metabolism – specifically a decrease in ability to maintain an electrochemical gradient, the endocochlear potential. However, direct measurements of metabolism across a lifespan in an auditory system are lacking. Even if metabolism does decrease with age, the question remains is it a cause of age-related auditory decline or simply correlative? All auditory systems across the animal kingdom share functional principles including ion pumping cells, auditory receptors, spiking auditory nerves and multiple supporting cells. Therefore, we used an insect, the desert locust,Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that although metabolism correlates with age-related auditory decline it is not causative.
Chromatin accessibility is a two-tier process regulated by transcription factor pioneering and enhancer activation
Authors: Brennan Kaelan J. , Weilert Melanie , Krueger Sabrina , Pampari Anusri , Liu Hsiao-Yun , Yang Ally W.H. , Hughes Timothy R. , Rushlow Christine A. , Kundaje Anshul , Zeitlinger Julia
Published: December 2022

Chromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it is difficult to differentiate between TFs that drive accessibility and those that do not. Deep learning models that learn complex sequence rules provide an unprecedented opportunity to dissect this problem. Using zygotic genome activation in theDrosophilaembryo as a model, we generated high-resolution TF binding and chromatin accessibility data, analyzed the data with interpretable deep learning, and performed genetic experiments for validation. We uncover a clear hierarchical relationship between the pioneer TF Zelda and the TFs involved in axis patterning. Zelda consistently pioneers chromatin accessibility proportional to motif affinity, while patterning TFs augment chromatin accessibility in sequence contexts in which they mediate enhancer activation. We conclude that chromatin accessibility occurs in two phases: one through pioneering, which makes enhancers accessible but not necessarily active, and a second when the correct combination of transcription factors leads to enhancer activation.
Shared neural codes of recognition memory
Authors: Ambrus Géza Gergely
Published: December 2022

Recognition memory research has identified several electrophysiological indicators of successful memory retrieval, known as old-new effects. These effects have been observed in different sensory domains using various stimulus types, but little attention has been given to their similarity or distinctiveness and the underlying processes they may share. Here, a data-driven approach was taken to investigate the temporal evolution of shared information content between different memory conditions using openly available EEG data from healthy human participants of both sexes, taken from six experiments. A test dataset involving personally highly familiar and unfamiliar faces was used. The results show that neural signals of recognition memory for face stimuli were highly generalized starting from around 200 ms following stimulus onset. When training was performed on non-face datasets, an early (around 200-300 ms) to late (post-400 ms) differentiation was observed over most regions of interest. Successful cross-classification for non-face stimuli (music and object/scene associations) was most pronounced in late period. Additionally, a striking dissociation was observed between familiar and remembered objects, with shared signals present only in the late window for correctly remembered objects, while cross-classification for familiar objects was successful in the early period as well. These findings suggest that late neural signals of memory retrieval generalize across sensory modalities and stimulus types, and the dissociation between familiar and remembered objects may provide insight into the underlying processes.
Structural basis of odorant recognition by a human odorant receptor
Authors: Billesbølle Christian B. , de March Claire A. , van der Velden Wijnand J. C. , Ma Ning , Tewari Jeevan , del Torrent Claudia Llinas , Li Linus , Faust Bryan , Vaidehi Nagarajan , Matsunami Hiroaki , Manglik Aashish
Published: December 2022

Our sense of smell enables us to navigate a vast space of chemically diverse odor molecules. This task is accomplished by the combinatorial activation of approximately 400 olfactory G protein-coupled receptors (GPCRs) encoded in the human genome1–3. How odorants are recognized by olfactory receptors (ORs) remains mysterious. Here we provide mechanistic insight into how an odorant binds a human olfactory receptor. Using cryogenic electron microscopy (cryo-EM), we determined the structure of active human OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an olfactory receptor. Molecular dynamics simulations demonstrate propionate-induced conformational changes in extracellular loop 3 to activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate OR, providing insight into how this large family of GPCRs enables our olfactory sense.
T cell development is regulated by high fidelity replication of mitochondrial DNA
Authors: Limper Candice B. , Bondah Narda , Zhu Daphne , Villanueva Alanis N. , Chukwukere Uchenna K. , Huang Weishan , August Avery
Published: December 2022

One of the most proliferative periods for T cells occurs during their development in the thymus. Increased DNA replication can result in increased DNA mutations in the nuclear genome, but also in mitochondrial genomes. A high frequency of mitochondrial DNA mutations can lead to abnormal mitochondrial function and have negative implications on human health. Furthermore, aging is accompanied by an increase in such mutations through oxidative damage and replication errors. Increased mitochondrial DNA mutations cause loss of mitochondrial protein function, and decrease energy production, substrates, and metabolites. Here we have evaluated the effect of increased mitochondrial DNA mutations on T cell development in the thymus. Using mice carrying a mutant mitochondrial DNA polymerase γ (PolG) that causes increased mitochondrial DNA mutations, we show that high fidelity replication of mitochondrial DNA is pivotal for proper T cell development. Reducing the fidelity of mitochondrial DNA replication results in a premature age-dependent reduction in the total number of CD4/CD8 double negative and double positive thymocytes. Analysis of mitochondrial density in thymocyte subpopulations suggests that this may be due to reduced proliferation in specific double negative stages. Taken together, this work suggests that T cell development is regulated by the ability of mitochondria to faithfully replicate their DNA.
The hippocampus binds movements to their temporal position in a motor sequence
Authors: Dolfen Nina , Reverberi Serena , Op de beeck Hans , King Bradley R. , Albouy Genevieve
Published: December 2022

A plethora of daily motor tasks consist of sequences of movements or steps that need to be performed in a specific order. Yet, it remains unclear how the brain represents sequential motor actions in a way that preserves their temporal order. Here, we used multivoxel pattern similarity analysis of functional Magnetic Resonance Imaging (fMRI) data acquired during motor sequence practice to investigate whether the hippocampus, a brain region known to support temporal order in the non-motor memory domain, represents information about the temporal order of sequential motor actions. We also examined such representation in other regions of the motor network (i.e., the premotor cortex (PMC), supplementary motor area (SMA), anterior superior parietal lobule (aSPL) and striatum) known for their critical role in motor sequence learning. Our results show that hippocampal activation patterns carried information about movements in their learned temporal position in the sequence (i.e., movement-position binding), but not about movements or positions in random movement patterns. In contrast, other ROIs showed evidence of binding in the sequence as well as movement (M1, SMA, PMC, putamen and aSPL) and position (aSPL and PMC) coding in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in M1, SMA and PMC but not in the putamen and aSPL, suggesting a specific involvement of these regions in movement-position binding. Altogether, our findings provide novel insight into the role of the hippocampus in the motor memory domain and point to its capacity to bind movements to their temporal position in a motor sequence. Our results also deepen our understanding of how striatal and cortical regions contribute to motor sequence learning via movement coding or movement-position binding.

Significance Statement

Consistent evidence collected over the last two decades indicates that the hippocampus - a brain structure traditionally associated to declarative memory - is critically involved in motor memory. Yet, the functional role and representational contribution of the hippocampus during motor learning remains to be elucidated. Using a multivariate functional MRI approach, we show here that the hippocampus binds movements to their temporal position in a learned sequence of actions. These results point towards the involvement of the hippocampus in preserving information about temporal order in motor memory - a process well described for declarative memories. We suggest that the ability of the hippocampus to encode temporal order during sequence learning is common across declarative and non-declarative memory systems.
Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum
Authors: Girgis Sophia T. , Adika Edem , Nenyewodey Felix E. , Senoo Jnr Dodzi K. , Ngoi Joyce M. , Bandoh Kukua , Lorenz Oliver , van de Steeg Guus , Harrott Alexandria J. R. , Nsoh Sebastian , Judge Kim , Pearson Richard D. , Almagro-Garcia Jacob , Saiid Samirah , Atampah Solomon , Amoako Enock K. , Morang’a Collins M. , Asoala Victor , Adjei Elrmion S. , Burden William , Roberts-Sengier William , Drury Eleanor , Pierce Megan L. , Gonçalves Sónia , Awandare Gordon A. , Kwiatkowski Dominic P. , Amenga-Etego Lucas N. , Hamilton William L.
Published: December 2022

Malaria is a global public health priority causing over 600,000 deaths annually, mostly young children living in Sub-Saharan Africa. Molecular surveillance can provide key information for malaria control, such as the prevalence and distribution of antimalarial drug resistance. However, genome sequencing capacity in endemic countries can be limited. Here, we have implemented an end-to-end workflow forP. falciparumgenomic surveillance in Ghana using Oxford Nanopore Technologies, targeting antimalarial resistance markers and the leading vaccine antigencircumsporozoite protein(csp). The workflow was rapid, robust, accurate, affordable and straightforward to implement, and could be deployed using readily collected dried blood spot samples. We found thatP. falciparumparasites in Ghana had become largely susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine (SP) resistance, and no evidence of artemisinin resistance. Multiple Single Nucleotide Polymorphism (SNP) differences from the vaccinecspsequence were identified, though their significance is uncertain. This study demonstrates the potential utility and feasibility of malaria genomic surveillance in endemic settings using Nanopore sequencing.
Early Seasonal Increases and Persistence in Relative Abundance of Potentially Toxic Cyanobacteria: Concerning Impacts of Extended Ice-Free Periods in Northern Temperate Lakes
Authors: Cameron Ellen S. , Müller Kirsten M. , Stone Mike , Buttle Jim , Leach Jason , Webster Kara , Emelko Monica B.
Published: December 2022

Cyanobacteria threaten public and ecosystem health globally through the production of secondary metabolites including potent toxins, and disruption of water treatment processes. Warmer water temperatures and high nutrient availability are key characteristics associated with the occurrence of cyanobacteria. There is typically concern of cyanobacteria blooms (e.g., visible biomass accumulations) occurring in the summer season of eutrophic systems. However, in this study, the proliferation of cyanobacteria in lakes across all seasons and in absence of visual biomass indicators of bloom condition was observed in three oligotrophic lakes of the Turkey Lakes Watershed (TLW) in Ontario, located within a sugar maple dominated forest on the Canadian Shield. Almost 40 years of ice phenology data showed that rising temperatures have led to significantly longer ice-free periods and aquatic growing seasons in TLW. Warming is especially evident in the autumn, with the onset of ice-on periods commencing significantly later in the year. Cyanobacterial communities in three interconnected temperate, oligotrophic lakes were characterized over an 18-month period from July 2018 to January 2020 (across 10 synoptic sampling events) using amplicon sequencing of the V4 region of the 16S rRNA gene. During the winter, there was low abundance or occasional absence of cyanobacteria; however, a non-photosynthetic basal lineage of cyanobacteria (Melainabacteria) was present during periods of ice cover. Notably, photosynthetic populations reappeared in the water column immediately following the loss of ice-cover—they were especially abundant in lakes with surficial geology and lake morphometry that favor greater availability of fine sediment and associated nutrients. Thus, this collective analysis demonstrates that the convergence of key abiotic and biotic factors—climate forcing of hydrological and biogeochemical processes, and intrinsic landscape features—enable increases in the relative abundance of potentially toxic cyanobacteria within the temperate forest biome of Canada over increasingly longer periods of time.
Glycogen-fuelled metabolism supports rapid Mucosal Associated Invariant T cell responses
Authors: Cassidy Féaron C. , Kedia-Mehta Nidhi , Bergin Ronan , Woodcock Andrea , Berisha Ardena , Bradley Ben M. , Booth Eva , Ryan Odhran K. , Sinclair Linda V. , O’Shea Donal , Hogan Andrew E.
Published: December 2022

Mucosal Associated Invariant T (MAIT) cells are a subset of unconventional T cells, which recognise a limited repertoire of ligands presented by the MHC class I-like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties and rapid effector functions, MAIT cells are emerging as attractive candidates for cancer-immunotherapy. In the current study, we demonstrate that MAIT cells are potent anti-tumour cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 hours. However, the metabolic processes supporting rapid MAIT cell anti-tumour responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 hours) cytokine production, as is oxidative phosphorylation. We show for the first time that MAIT cells have the machinery required to make and metabolize glycogen, and demonstrate that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show for the first time that glycogen-fuelled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications in their use as an immunotherapeutic agent.
Systems Level Identification of a Matrisome-Associated Macrophage Polarization State in Multi-Organ Fibrosis
Authors: Huang Kevin Y. , Mishra Kunal , Park Harry , Yi Xie , Ouyang John F. , Petretto Enrico , Behmoaras Jacques
Published: December 2022

Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unraveled multi-organ heterogeneity of macrophages in healthy and fibrotic human disease suggest that tissue resident macrophages, expressing osteopontin (SPP1), associate with lung and liver fibrosis. However, the conservation of this SPP1+ macrophage population across different tissues, and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 13 single cell RNA-sequencing datasets to profile 225,985 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin and endometrium, we extended the association of SPP1+ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodeling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarization state within SPP1+ macrophages. Importantly, the MAM polarization state follows a differentiation trajectory from SPP1+ macrophages, which was conserved across all fibrotic tissues and driven by NFATC1 and HIVEP3 regulons. Unlike SPP1+ macrophages, the MAM polarization state shows a positive association with ageing in mice and humans, and across multiple tissues during homeostasis. These results suggest an advanced, age-dependent polarization state of SPP1+ macrophages in fibrotic tissues as a result of prolonged inflammatory cues within each tissue microenvironment.
Integrative modeling of guanylate binding protein dimers
Authors: Schumann Wibke , Loschwitz Jennifer , Reiners Jens , Degrandi Daniel , Pfeffer Klaus , Stühler Kai , Poschmann Gereon , Smits Sander H.J. , Strodel Birgit
Published: December 2022

Guanylate binding proteins (GBPs) are interferon-γ-activated large GTPases, effective against intracellular pathogens likeToxoplasma gondii. Their host-protective functions require oligomerization, however, the oligomer structures have not been completely resolved yet. Here, we provide dimer models for hGBP1 and the murine GBPs 2 and 7 (mGBP2 and mGBP7) based on integrative modeling that involves the crystal structure of the G domain dimer of hGBP1, cross-linking mass spectrometry (XL-MS), small angle X-ray scattering (SAXS), protein-protein docking, and molecular dynamics (MD) simulations of hGBP1, mGBP2 and mGBP7. We first compare the sequences and protein dynamics of the monomeric hGBP1, mGBP2, and mGBP7, finding that the M/E domain of all three proteins is highly mobile featuring a hinge movement, yet this motion is less pronounced in mGBP7 while its GTPase (G) domain is more flexible. These differences can be explained by the variations in the sequences between mGBP7 and hGBP1/mGBP2 and extend to their dimers. While hGBP1 and its close orthologue mGBP2 dimerize via their G domains, mGBP7 shows a variety of possible dimer structures, among them parallel and crossed-stalk conformations. The G domain is only partly involved in mGBP7 dimerization, which provides a rational why mGBP7, unlike hGBP1 and mGBP2, can dimerize in the absence of GTP. The different GBP dimer structures, which still exhibit hinge movements to certain degrees, are expected to encode diverging functions, such as a destabilization of pathogenic membranes or fusion of the parasitophorous vacuole membrane with the autophagic machinery.
Harnessing photosynthetic bacterium for light-powered biocatalysis
Authors: Zhang Yang , Yuan Jifeng
Published: December 2022

The traditional whole-cell biocatalysis typically utilizes the heterotrophic microbes as the biocatalyst, which requires carbohydrates to power the cofactor (ATP, NAD(P)H) regeneration. In this study, we sought to harness purple non-sulfur photosynthetic bacterium (PNSB) as the biocatalyst to achieve light-driven cofactor regeneration for cascade biocatalysis. We substantially improved the performance of PNSB-based biocatalysis by using a highly active and conditional expression system, blocking the side-reactions, controlling the feeding strategy, and attenuating the light shading effect. We found that 50 mM ferulic acid could be completely converted to vanillyl alcohol in the recombinant strain, reaching 7.7 g/L vanillyl alcohol. In addition, >99.9% conversion ofp-coumaric acid top-hydroxybenzoic alcohol (6.21 g/L) was similarly achieved under light-anaerobic conditions. Moreover, we examined the isoprenol utilization pathway (IUP) for pinene synthesis and 13.81 mM pinene (1.88 g/L) with 92.1% conversion rate from isoprenol was obtained. Taken together, these results suggested that PNSB could be a promising host for light-powered biotransformation, which offers an efficient approach for synthesizing value-added chemicals in a green and sustainable manner.
Walking bumblebees see faster
Authors: Rother Lisa , Müller Robin , Kirschenmann Erwin , Kaya-Zeeb Sinan , Thamm Markus , Pfeiffer Keram
Published: December 2022

The behavioral state of an animal has profound effects on neuronal information processing. Locomotion changes the response properties of visual interneurons in the insect brain, but it is still unknown if it also alters the response properties of photoreceptors. Photoreceptor responses become faster at higher temperatures. It has therefore been suggested that thermoregulation in bees and other insects could improve temporal resolution in vision, but direct evidence for this idea has so far been missing. Here we compared electroretinograms (ERGs) from the compound eyes of tethered bumblebees that were either sitting still or were walking on an air supported ball. We found that the visual processing speed strongly increased when the bumblebees were walking. By monitoring the bumblebees’ eye temperature during our recordings, we saw that the increase in response speed was in synchrony with a rise of the eye temperature. By artificially heating the bee’s head, we show that the walking induced temperature increase of the visual system is sufficient to explain the rise in processing speed. We also show that walking accelerates the visual system to the equivalent of a 14-fold increase in light intensity. We conclude that the walking-induced rise in temperature accelerates the processing of visual information in bumblebees, which is an ideal strategy to process the increased information flow during locomotion.
Hippocampal neuronal synchronization in the rat - Dissociation of perception from associative learning
Authors: Kim Kayeon , Nokia Miriam S. , Palva J. Matias , Palva Satu
Published: December 2022

Learning requires flexible switching between perceiving and encoding external sensory stimuli, making associations with representations already stored in memory (retrieval) and acting accordingly to adapt to the environment. Hippocampus is known to be central in creating mnemonic representations, but how it could support the integration of these processes of memory encoding and retrieval during repetitive learning experiences has remained unknown. In this study, we recorded local-field potentials (LFPs) from the dorsal hippocampus during classical trace eyeblink conditioning in rats. An auditory conditioned stimulus (CS) was followed by a periorbital shock-unconditioned stimulus (US). From the LFPs, we separated hippocampal oscillations that were linked with the variation in the trial-by-trial processing of the CS from those linked with the gradual learning of the CS-US association over daily sessions of training. Short latency transient theta and gamma band oscillations were associated with learning so that both the oscillation amplitudes (strength) and phase locking increased as a function of training. In contrast, long-latency sustained alpha and beta oscillations were associated with perception of CS. These data show divergent oscillatory neural signatures for perception and learning in hippocampal subfields.
Differential transpiration between pods and leaves during stress combination in soybean
Authors: Sinha Ranjita , Shostak Benjamin , Induri Sai Preethi , Sen Sidharth , Zandalinas Sara I. , Joshi Trupti , Fritschi Felix B. , Mittler Ron
Published: December 2022

Climate change is causing an increase in the frequency and intensity of droughts, heat waves, and their combinations, diminishing agricultural productivity and destabilizing societies worldwide. We recently reported that during a combination of water deficit (WD) and heat stress (HS) stomata on leaves of soybean plants are closed, while stomata on flowers are open. This unique stomatal response was accompanied by differential transpiration (higher in flowers, while lower in leaves) that cooled flowers during a combination of WD+HS. Here we reveal that developing pods of soybean plants subjected to a combination of WD+HS use a similar acclimation strategy of differential transpiration to reduce internal pod temperature by about 4°C. We further show that enhanced expression of transcripts involved in abscisic acid degradation accompanies this response, and that preventing pod transpiration by sealing stomata causes a significant increase in internal pod temperature. Using an RNA-Seq analysis of pods developing on plants subjected to WD+HS, we also show that the response of pods to WD, HS, or WD+HS is distinct from that of leaves or flowers. Interestingly, we report that although flower, pod and seed numbers per plant are decreased under conditions of WD+HS, seed mass of plants subjected to WD+HS is larger than that of plants subjected to HS, and number of seeds with suppressed/aborted development is lower in WD+HS compared to HS. Taken together our findings reveal that differential transpiration occurs in pods of soybean plants subjected to WD+HS and that this process limits heat-induced damage to seed production.

One sentence summary

Differential transpiration between pods and leaves of soybean plants subjected to a combination of water deficit and heat stress buffers internal pod temperature.