bluuebunny/crossref_metadata_2025 huggingface dataset:
Horizontal Transfer and Evolution of the Biosynthetic Gene Cluster for Benzoxazinoid
Authors: Wu Dongya , Jiang Bowen , Ye Chu-Yu , Timko Michael P. , Fan Longjiang
Published: December 2021

Benzoxazinoids are a class of protective and allelopathic plant secondary metabolites, first identified in maize (Zea mays) and subsequently shown to be encoded by a biosynthetic gene cluster (BGC), the Bx cluster. Data mining of mining 40 high-quality grass genomes identified complete Bx clusters (containing genes Bx1 to Bx5 and Bx8) in three genera (Zea, Echinochloa and Dichanthelium) in the Panicoideae and partial clusters in the Triticeae. The Bx cluster originated from gene duplication of native analogues of Bx genes and chromosomal translocation. An ancient Bx cluster including additional Bx genes (e.g., Bx6) is found in ancestral Panicoideae. The ancient Bx cluster was gained by the Triticeae ancestor via a horizontal transfer (HT) event from the ancestral Panicoideae and later separated into three parts on different chromosomes. Bx6 appears to have been under less constrained selection during evolution of the Panicoideae as evidenced by the fact that was translocated ∼1.31-Mb away from the Bx cluster in Z. mays, moved to other chromosomes in Echinochloa, and even lost in Dichanthelium. Further investigation indicated that intense selection and polyploidization shaped the evolutionary trajectory of the Bx cluster in the grass family. This study provides the first case of HT of BGCs among plants and sheds new insights on the evolution of BGCs.

Significance

Biosynthetic gene clustering and horizontal gene transfer are two evolutionary inventions for rapid adaption by organisms. Horizontal transfer of a gene cluster has been reported in fungi and bacteria, but not in plants up to now. By mining the genomes of 40 monocot species, we deciphered the organization of Bx gene cluster, a biosynthetic gene cluster for benzoxazinoids in grasses. We found that the Bx cluster was formed by gene duplication of native analogues of individual Bx genes and directional translocation. More importantly, the Bx cluster in Triticeae was inherited from the Panicoideae via horizontal transfer. Compared with the native analogues, Bx clusters in grasses show constrained purifying selection underscoring their significance in environmental adaption.
Access to healthcare as an important moderating variable for understanding geography of immunity levels for COVID-19 - preliminary insights from Poland
Authors: Jarynowski Andrzej , Belik Vitaly
Published: December 2021

Background

Biases in COVID-19 burden and uncertainty in estimation of the corresponding epidemiologic indexes is a known and common phenomenon in infectious diseases. We investigated to what extent healthcare access (HCA) related supply/demand interfered with registered data on COVID-19 in Poland.

Material and methods

We run a multiple linear regression model with interactions to explain geographic variation in seroprevalence, hospitalizations (on voivodeship – NUTS-2 level) and current (beginning of the 4th wave – 15.09-21.11.2021) case notifications/crude mortality (on poviat – old NUTS-4 level). We took vaccination coverage and cumulative case notifications up to the so called 3rd wave as predictor variables and supply/demand (HCA) as moderating variables.

Results

HCA with interacting terms (mainly demand) explained to the great extent the variance of current incidence and most variance of current mortality. HCA (mainly supply) is significantly moderating cumulative case notifications till the 3rd wave explaining the variance in seroprevalence and hospitalization.

Conclusions

Seeking causal relations between vaccination-or infection-gained immunity level and current infection dynamics could be misleading without understanding socio-epidemiologic context such as the moderating role of HCA (sensu lato). After quantification, HCA could be incorporated into epidemiologic models for improved prediction of real disease burden.
Dose-response relationship of extended-release methylphenidate for ADHD in adults: post-hoc analysis based on a systematic review
Authors: Boesen K , Jørgensen KJ , Gøtzsche PC
Published: December 2021

Objective

To assess potential dose-response relationships of extended-release methylphenidate for ADHD in adults on efficacy outcomes.

Study design and setting

Post-hoc analysis based on a systematic review of extended-release methylphenidate (https://doi.org/10.1002/14651858.CD012857). Using data from clinical trials comparing multiple fixed-dose methylphenidate groups with placebo, we conducted subgroup meta-analyses for available efficacy outcomes.

Results and conclusion

Five trials used a fixed-dose design with multiple methylphenidate groups receiving different doses. All trials were pivotal industry sponsored studies conducted to obtain marketing authorisation. We analysed four efficacy outcomes: Selfrated ADHD symptoms (5 trials, 1807 participants), investigator-rated ADHD symptoms (5 trials, 1904 participants), quality of life (4 trials, 1158 participants), and peer-rated ADHD symptoms (2 trials, 879 participants). There were no dose-response relationships for any outcome.
Colonic Oxygen Microbubbles Augment Systemic Oxygenation and CO2 Removal in a Porcine Smoke Inhalation Model of Severe Hypoxia
Authors: Mountford Paul. A. , Leiphrakpam Premila. D. , Weber Hannah. R. , McCain Andrea , Scribner Robert. M. , Scribner Robert. T. , Duarte Ernesto M. , Chen Jie , Borden Mark. A. , Buesing Keely. L.
Published: December 2021

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n=6 colonic OMB, n=6 no treatment) ranging from 39-51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 % ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest x-ray. Colonic OMB infusion (75 – 100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2% ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9% ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.

One Sentence Summary

Enteral oxygen microbubbles increase systemic oxygen and decrease carbon dioxide levels in acutely hypoxic pigs after smoke inhalation-induced respiratory failure.
Human neural networks with sparse TDP-43 pathology reveal NPTX2 misregulation in ALS/FTLD
Authors: Hruska-Plochan Marian , Betz Katharina M. , Ronchi Silvia , Wiersma Vera I. , Maniecka Zuzanna , Hock Eva-Maria , Laferriere Florent , Sahadevan Sonu , Hoop Vanessa , Delvendahl Igor , Panatta Martina , van der Bourg Alexander , Bohaciakova Dasa , Frontzek Karl , Aguzzi Adriano , Lashley Tammaryn , Robinson Mark D. , Karayannis Theofanis , Mueller Martin , Hierlemann Andreas , Polymenidou Magdalini
Published: December 2021

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating these age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1,2, which involve human-specific mechanisms3–6 that cannot be directly studied in animal models. To explore the emergence and consequences of TDP-43 pathologies, we generated iPSC-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors7. Single-cell transcriptomics (scRNA-seq) and comparison to independent NSCs8, showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks. Neuronal and glial maturation in iCoMoNSC-derived cultures was similar to that of cortical organoids9. Overexpression of wild-type TDP-43 in a minority of iCoMoNSC-derived neurons led to progressive fragmentation and aggregation, resulting in loss of function and neurotoxicity. scRNA-seq revealed a novel set of misregulated RNA targets coinciding in both TDP-43 overexpressing neurons and patient brains exhibiting loss of nuclear TDP-43. The strongest misregulated target encoded for the synaptic protein NPTX2, which was consistently misaccumulated in ALS and FTLD patient neurons with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby highlighting a new pathway of neurotoxicity.
Volatile-mediated signaling induces resistance of barley against infection with the biotrophic fungusBlumeria graminisf.sp.hordei
Authors: Laupheimer Silvana , Proels Reinhard , Unsicker Sybille B. , Hückelhoven Ralph
Published: December 2021

Plants have evolved a vast variety of secondary metabolites to counteract biotic stress. Volatile organic compounds (VOCs) are carbon-based molecules induced by herbivore attack or pathogen infection. A mixture of plant VOCs is released for direct or indirect plant defense, plant-plant or plant-insect communication. Recent studies suggest that VOCs can also induce biotic stress resistance in distant organs and neighboring plants. Among other VOCs, green leaf volatiles (GLVs) are quickly released by plant tissue after the onset of herbivory or wounding.

We analysed VOCs emitted by 13-day old barley plants (Hordeum vulgareL.) after mechanical wounding using passive absorbers and TD-GC/MS detection. We investigated the influence of pure (Z)-3-hexenyl acetate (Z3HAC) as well as complex VOCs from wounded barley plants on the barley - powdery mildew interaction by pre-exposure in a static and a dynamic headspace connected to a powdery mildew susceptibility assay.

GLVs dominated the volatile profile of wounded barley plants with Z3HAC as the most prominent compound. Pre-exposure with Z3HAC resulted in induced resistance of barley against fungal infection. Barley complex volatiles emitted after mechanical wounding, similarly, enhanced resistance in receiver plants.

We found volatile-induced modification of the interaction towards an enhanced resistance against fungal infection. In addition, Z3HAC triggered a modulation of the alcohol dehydrogenase isoenzyme activity in receiver plants, a physiological response that possibly contributes to induced resistance. Plant-originated volatile metabolites could be a useful supplementation for future agronomic or horticultural practices.

Highlight

Volatile-induced modification of the barley-powdery mildew interaction towards an enhanced resistance against fungal infection.
Altered Task Demands Lead to a Division of Labor for Sensory and Cognitive Processing in the Middle Temporal Area
Authors: Scott Hayden , Wimmer Klaus , Pasternak Tatiana , Snyder Adam C.
Published: December 2021

Neurons in the primate Middle Temporal (MT) area signal information about visual motion and work together with the lateral prefrontal cortex (LPFC) to support memory-guided comparisons of visual motion direction. These areas are reciprocally connected, and both contain neurons that signal visual motion direction in the strength of their responses. Previously, LPFC was shown to display marked changes in stimulus coding with altered task demands, including changes in selectivity for motion direction, trial-to-trial variability in responses, and comparison effects. Since MT and LPFC are directly interconnected, we sought to determine if MT neurons display similar dependence on task demands. We found that active participation in a motion direction comparison task affected both sensory and non-sensory activity in MT neurons. In fact, neurons that became less-selective for motion direction during the active task showed increased signalling for cognitive aspects of the task. This heterogeneity in neural modification with heightened task demands suggests a division of labor in MT, whereby sensory and cognitive signals are both heightened in different subpopulations of neurons.
The arousal-motor hypothesis of dopamine function: evidence that dopamine facilitates reward seeking in part by maintaining arousal
Authors: Kaźmierczak Marcin , Nicola Saleem M.
Published: December 2021

Dopamine facilitates approach to reward via its actions on dopamine receptors in the nucleus accumbens. For example, blocking either D1 or D2 dopamine receptors in the accumbens reduces the proportion of reward-predictive cues to which rats respond with cued approach. Recent evidence indicates that accumbens dopamine also promotes wakefulness and arousal, but the relationship between dopamine’s roles in arousal and reward seeking remains unexplored. Here, we show that the ability of systemic or intra-accumbens injections of the D1 antagonist SCH23390 to reduce cued approach to reward depends on the animal’s state of arousal. Handling the animal, a manipulation known to increase arousal, was sufficient to reverse the behavioral effects of the antagonist. In addition, SCH23390 reduced spontaneous locomotion and increased time spent in sleep postures, both consistent with reduced arousal, but also increased time spent immobile in postures inconsistent with sleep. In contrast, the ability of the D2 antagonist haloperidol to reduce cued approach was not reversible by handling. Haloperidol reduced spontaneous locomotion but did not increase sleep postures, instead increasing immobility in non-sleep postures. We place these results in the context of the extensive literature on dopamine’s contributions to behavior, and propose the arousal-motor hypothesis. This novel synthesis, which proposes that two main functions of dopamine are to promote arousal and facilitate motor behavior, accounts both for our findings and many previous behavioral observations that have led to disparate and conflicting conclusions.
Directional Tuning of Phase Precession Properties in the Hippocampus
Authors: Yiu Yuk-Hoi , Leutgeb Jill K. , Leibold Christian
Published: December 2021

Running direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2 and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a place field’s preferred firing rate direction spikes are more likely to undergo theta phase precession and, hence, more strongly impact paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effects are associated with differences in theta phase distributions, and are more prominent in CA3 than CA1. We thus hypothesize that intrinsic spiking is most prominent when the directionally modulated sensory-motor drive of hippocampal firing rates is minimal, suggesting that extrinsic and intrinsic sequences contribute to phase precession as two distinct mechanisms.
Increased context adjustment is associated with auditory sensitivities but not with autistic traits
Authors: Randeniya R. , Mattingley J. B. , Garrido M. I.
Published: December 2021

Bayesian models of autism suggest that disruptions in context-sensitive prediction error weighting may underpin sensory perceptual alterations, such as hypersensitivities. We used an auditory oddball paradigm with pure tones arising from high or low uncertainity contexts to determine whether autistic individuals display differences in context adjustment relative to neurotypicals. We did not find group differences in early prediction error responses indexed by mismatch negativity. However, the autism group had larger evoked responses to outliers, at 300ms latency suggesting a greater reorienting of attention to surprising sounds. A dimensional approach revealed a positive correlation between context-dependent prediction errors and auditory sensitivities, but not with autistic traits. These findings suggest that autism studies may benefit from accounting for sensory sensitivities in group comparisons.

Lay Summary

We find no differences in brain responses (EEG amplitudes) between autistic and neurotypical adults when listening to two contexts of tone patterns. However, we find a larger difference in the EEG amplitude when shifting between low to high uncertainity streams of tones, as sensory sensitivities (but not autistic traits) increase. These findings show that perceptual alterations maybe a function of sensory sensitivities, but not necessarily autistic traits. We suggest that future EEG studies in autism may benefit from accounting for sensory sensitivities.
Age- and sex-related differences in baboon (Papio anubis) gray matter covariation
Authors: Mulholland M. M. , Meguerditchian A. , Hopkins W. D.
Published: December 2021

Age-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer’s disease-like pathology and cognitive declines with age and are an underutilized model for studies of aging. To determine age-related differences in gray matter covariation of 89 olive baboons (Papio anubis), we used source-based morphometry (SBM) to analyze data from magnetic resonance images. We hypothesized that we would find significant age effects in one or more SBM components, particularly those which include regions influenced by age in humans and other nonhuman primates (NHPs). A multivariate analysis of variance revealed that individual weighted gray matter covariation scores differed across the age classes. Elderly baboons contributed significantly less to gray matter covariation components including the brainstem, superior parietal cortex, thalamus, and pallidum compared to juveniles, and middle and superior frontal cortex compared to juveniles and young adults (p<0.05). Future studies should examine the relationship between the changes in gray matter covariation reported here and age-related cognitive decline.
Geographic variation in larval cold tolerance and exposure across the invasion front of a widely established forest insect
Authors: Hafker Petra , Thompson Lily M. , Walter Jonathan A. , Parry Dylan , Grayson Kristine L.
Published: December 2021

As the global climate changes, high and low temperature extremes can drive changes in species distributions. Across the range of a species, thermal tolerance can experience plasticity and may undergo selection, shaping resilience to temperature stress. In this study, we measured variation in the lower thermal tolerance of early instar larvae of an invasive forest insect, Lymantria dispar dispar L. (Lepidoptera: Erebidae), using populations sourced from the climatically diverse invasion of the Eastern United States. In two chill coma recovery experiments, we recorded recovery time following a period of exposure to a non-lethal cold temperature. A third experiment quantified growth responses after chill coma recovery to evaluate sublethal effects. Our results indicate that cold tolerance is linked to regional climate, with individuals from cold climate populations recovering faster from chill coma. While this geographic gradient is seen in many species, detecting this pattern is notable for an introduced species founded from a single point-source introduction. We demonstrate that the cold temperatures used in our experiments occur in nature from cold snaps after spring hatching, but negative impacts to growth and survival appear low. We expect that population differences in cold temperature performance manifest more from differences in temperature-dependent growth than acute exposure. Evaluating intraspecific variation in cold tolerance increases our understanding of the role of climatic gradients on the physiology of an invasive species, and contributes to tools for predicting further expansion.

Summary Statement

Chill coma recovery experiments demonstrate geographic variation in cold temperature tolerance for a widespread invasive species, and the risk of early season exposure differs across the invasion front.
Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by in vitro Cellular Studies and in vivo PET Imaging
Authors: Zhang Hannah J. , Zammit Matthew , Kao Chien-Min , Govind Anitha P , Mitchell Samuel , Holderman Nathanial , Bhuiyan Mohammed , Freifelder Richard , Zhuang Xiaoxi , Mukherjee Jogeshwar , Chen Chin-Tu , Green William N.
Published: December 2021

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membranepermeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKa and high-affinity for α4β2-type nicotinic receptors (α4β2Rs) are trapped in intracellular acidic vesicles containing α4β2Rs in vitro. Nicotine, with lower pKa and α4β2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in vivo in mouse brain and identifying the trapping brain organelle in vitro as Golgi satellites (GSats). Two PET 18F-labelled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKa and affinity and [18F]Nifene with nicotine-like pKa and affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in α4β2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to α4β2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals were eliminated in β2 subunit knockout mice or by acute nicotine injections demonstrating binding to sites on β2-containing receptors. Chloroquine, which dissipates GSat pH gradients, reduced [18F]2-FA distributions while having little effect on [18F]Nifene distributions in vivo consistent with only [18F]2-FA trapping in GSats. These results are further supported by in vitro findings where dissipation of GSat pH gradients blocks 2-FA trapping in GSats without affecting Nifene. By combining in vitro and in vivo imaging, we mapped both the brain-wide and subcellular distributions of weak-base nicotinic receptor ligands. We conclude that ligands, such as varenicline, are trapped in neurons in α4β2R-containing GSats, which results in very slow release long after nicotine is gone after smoking.

Significance

Mechanisms of nicotine addiction remain poorly understood. An earlier study using in vitro methods found that the anti-smoking nicotinic ligand, varenicline (Chantix) was trapped in α4β2R-containing acidic vesicles. Using a fluorescent labeled high-affinity nicotinic ligand, this study provided evidence that these intracellular acidic vesicles were α4β2R-containing Golgi satellites. In vivo PET imaging with F-18 labeled nicotinic ligands provided additional evidence that differences in PET ligand trapping in acidic vesicles were the cause of differences in PET ligand kinetics and subcellular distributions. These findings combining in vitro and in vivo imaging revealed new mechanistic insights into the kinetics of weak base PET imaging ligands and the subcellular mechanisms underlying nicotine addiction.
DISA tool: discriminative and informative subspace assessment with categorical and numerical outcomes
Authors: Alexandre Leonardo , Costa Rafael S. , Henriques Rui
Published: December 2021

Motivation

Pattern discovery and subspace clustering play a central role in the biological domain, supporting for instance putative regulatory module discovery from omic data for both descriptive and predictive ends. In the presence of target variables (e.g. phenotypes), regulatory patterns should further satisfy delineate discriminative power properties, well-established in the presence of categorical outcomes, yet largely disregarded for numerical outcomes, such as risk profiles and quantitative phenotypes.

Results

DISA (Discriminative and Informative Subspace Assessment), a Python software package, is proposed to assess patterns in the presence of numerical outcomes using well-established measures together with a novel principle able to statistically assess the correlation gain of the subspace against the overall space. Results confirm the possibility to soundly extend discriminative criteria towards numerical outcomes without the drawbacks well-associated with discretization procedures. A case study is provided to show the properties of the proposed method.

Availability

DISA is freely available at https://github.com/JupitersMight/DISA under the MIT license.

Contact

{leonardoalexandre@tecnico.ulisboa.pt,rmch@tecnico.ulisboa.pt} and {rs.costa@fct.unl.pt}
A direct high-throughput protein quantification strategy facilitates discovery and characterization of a celastrol-derived BRD4 degrader
Authors: Payne N. Connor , Maksoud Semer , Tannous Bakhos A. , Mazitschek Ralph
Published: December 2021

We describe a generalizable time-resolved Förster resonance energy transfer (TR-FRET)-based platform to profile the cellular action of heterobifunctional degraders (or proteolysis-targeting chimeras; PROTACs), capable of both accurately quantifying protein levels in whole cell lysates in less than 1 h and measuring small-molecule target engagement to en-dogenous proteins, here specifically for human bromodomain-containing protein 4 (BRD4). The detection mix consists of a single primary antibody targeting the protein of interest, a luminescent donor-labeled anti-species nanobody, and a fluorescent acceptor ligand. Importantly, our strategy can readily be applied to other targets of interest and will greatly facilitate the cell-based profiling of small molecule inhibitors and PROTACs in high-throughput format with unmodified cell lines. We further-more validate our platform in the characterization of celastrol, ap-quinone methide-containing pentacyclic triterpenoid, as a broad cysteine-targeting E3 ubiquitin ligase warhead for potent and efficient targeted protein degradation.
Nanotrap Particles Improve Nanopore Sequencing of SARS-CoV-2 and Other Respiratory Viruses
Authors: Andersen P , Barksdale S , Barclay RA , Smith N , Fernandes J , Besse K , Goldfarb D , Barbero R , Dunlap R , Jones-Roe T , Kelly R , Miao S , Ruhunusiri C , Munns A , Mosavi S , Sanson L , Munns D , Sahoo S , Swahn O , Hull K , White D , Kolb K , Noroozi F , Seelam J , Patnaik A , Lepene B
Published: December 2021

Presented here is a magnetic hydrogel particle enabled workflow for capturing and concentrating SARS-CoV-2 from diagnostic remnant swab samples that significantly improves sequencing results using the Oxford Nanopore Technologies MinION sequencing platform. Our approach utilizes a novel affinity-based magnetic hydrogel particle, circumventing low input sample volumes and allowing for both rapid manual and automated high throughput workflows that are compatible with nanopore sequencing. This approach enhances standard RNA extraction protocols, providing up to 40x improvements in viral mapped reads, and improves sequencing coverage by 20-80% from lower titer diagnostic remnant samples. Furthermore, we demonstrate that this approach works for contrived influenza virus and respiratory syncytial virus samples, suggesting that it can be used to identify and improve sequencing results of multiple viruses in VTM samples. These methods can be performed manually or on a KingFisher Apex system.
Temporal response characterization across individual multiomics profiles of prediabetic and diabetic subjects
Authors: Zheng Minzhang , Piermarocchi Carlo , Mias George I.
Published: December 2021

Longitudinal deep multi-omics profiling, which combines biomolecular, physiological, environmental and clinical measures data, shows great promise for precision health. However, integrating and understanding the complexity of such data remains a big challenge. Here we propose a bottom-up framework starting from assessing single individuals’ multi-omics time series, and using individual responses to assess multi-individual grouping based directly on similarity of their longitudinal deep multi-omics profiles. We applied our method to individual profiles from a study profiling longitudinal responses in type 2 diabetes mellitus. After generating periodograms for individual subject omics signals, we constructed within-person omics networks and analyzed personal-level immune changes. The results showed that our method identified both individual-level responses to immune perturbation, and the clusters of individuals that have similar behaviors in immune response and which was associated to measures of their diabetic status.
Ongoing transposition in cell culture reveals the phylogeny of diverse Drosophila S2 sub-lines
Authors: Han Shunhua , Dias Guilherme , Basting Preston J. , Nelson Michael G. , Patel Sanjai , Marzo Mar , Bergman Casey M.
Published: December 2021

Cultured cells are widely used in molecular biology despite poor understanding of how cell line genomes change in vitro over time. Previous work has shown that Drosophila cultured cells have a higher transposable element (TE) content than whole flies, but whether this increase in TE content resulted from an initial burst of transposition during cell line establishment or ongoing transposition in cell culture remains unclear. Here we sequence the genomes of 25 sub-lines of Drosophila S2 cells and show that TE insertions provide abundant markers for the phylogenetic reconstruction of diverse sub-lines in a model animal cell culture system. Analysis of DNA copy number evolution across S2 sub-lines revealed dramatically different patterns of genome organization that support the overall evolutionary history reconstructed using TE insertions. Analysis of TE insertion site occupancy and ancestral states support a model of ongoing transposition dominated by episodic activity of a small number of retrotransposon families. Our work demonstrates that substantial genome evolution occurs during long-term Drosophila cell culture, which may impact the reproducibility of experiments that do not control for sub-line identity.
Genome-wide identification and analyses of tomato (Solanum lycopersicum L.) high-affinity nitrate transporter 2 (NRT2) family genes and their responses to drought and salinity
Authors: Akbudak M. Aydın , Filiz Ertugrul , Çetin Durmuş
Published: December 2021

High-affinity nitrate transporter 2 (NRT2) proteins have vital roles in nitrate (NO3-) uptake and translocation in plants. The gene families coding NRT2 proteins have been identified and functionally characterized in many plant species. However, no systematic identification of NRT2 family members have been reported in tomato (Solanum lycopersicum). There is also little known about their expression profiles under environmental stresses. Accordingly, the present study aimed to identify NRT2 gene family in the tomato genome; then, investigate them in detail through bioinformatics, physiological and expression analyses. As a result, four novel NRT2 genes were identified in the tomato genome, all of which contain the same domain belonging to the Major Facilitator Superfamily (PF07690). The co-expression network of SlNRT genes revealed that they were co-expressed with several other genes in many different molecular pathways including transport, photosynthesis, fatty acid metabolism and amino acid catabolism. Programming many crucial physiological and metabolic pathways, various numbers of phosphorylation sites were predicted in the NRT2 proteins.
A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes
Authors: Toh H. , Yang C. , Formenti G. , Raja K. , Yan L. , Tracey A. , Chow W. , Howe K. , Bergeron L.A. , Zhang G. , Haase B. , Mountcastle J. , Fedrigo O. , Fogg J. , Kirilenko B. , Munegowda C. , Hiller M. , Jain A. , Kihara D. , Rhie A. , Phillippy A.M. , Swanson S. , Jiang P. , Clegg D.O. , Jarvis E.D. , Thomson J.A. , Stewart R. , Chaisson M.J.P. , Bukhman Y.V.
Published: December 2021

The Nile rat (Avicanthis niloticus) is an important animal model for biomedical research, including the study of diurnal rhythms and type 2 diabetes. Here, we report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3,613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including those that affect genes associated with type 2 diabetes and metabolic dysfunctions. These include 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Our findings reflect the exceptional level of genomic detail present in this assembly, which will greatly expand the potential of the Nile rat as a model organism for genetic studies.
People with nicotine use-disorder exhibit more prefrontal activity during preparatory control but reduced anterior cingulate activity during reactive control
Authors: Kalhan Shivam , Evelyn Chen Li Peng , Garrido Marta I. , Hester Robert
Published: December 2021

Reduced inhibitory control and a hypersensitivity to reward are key deficits in drug-dependents, however, they tend to be studied in isolation. Here we seek to understand the neural processes underlying control over reward and how this is different in people with a nicotine use disorder (pNUD). A novel variant of the monetary incentive delay task was performed by pNUD (n = 20) and non-smokers (n = 20), where we added a stop-signal component such that participants had to inhibit prepotent responses to earn a larger monetary reward. Brain activity was recorded using functional magnetic resonance imaging (fMRI). We estimated stop signal reaction times (SSRT), an indicator of impulsivity, and correlated these with brain activity. Inhibitory accuracy scores did not differ between the control group and pNUD. However, pNUD had slower SSRTs, suggesting that they may find it harder to inhibit responses. Brain data revealed that pNUD had greater preparatory control activity in the middle frontal gyrus and inferior frontal gyrus prior to successful inhibitions over reward. In contrast, non-smokers had greater reactive control associated with more activity in the anterior cingulate cortex during these successful inhibitions. SSRT-brain activity correlations revealed that pNUD engaged more control related prefrontal brain regions when SSRTs are slower. Overall, whilst the inhibition accuracy scores were similar between groups, differential neural processes and strategies were used to successfully inhibit a prepotent response. The findings suggest that increasing preparatory control in pNUD may be one possible treatment target in order to increase inhibitory control over reward.
Boosting serotonin increases information gathering by reducing subjective cognitive costs
Authors: Michely Jochen , Martin Ingrid M. , Dolan Raymond J. , Hauser Tobias U.
Published: December 2021

Serotonin is implicated in the valuation of aversive costs, such as delay or physical effort. However, its role in governing sensitivity to cognitive effort, for example deliberation costs during information gathering, is unclear. We show that week-long treatment with a serotonergic antidepressant enhances a willingness to gather information when trying to maximize reward. Using computational modelling, we show this arises from a diminished sensitivity to subjective deliberation costs during the sampling process. This result is consistent with the notion that serotonin alleviates sensitivity to aversive costs in a domain-general fashion, with implications for its potential contribution to a positive impact on motivational deficits in psychiatric disorders.
D-amphetamine maintenance therapy reduces cocaine use in female rats
Authors: Ndiaye Ndeye Aissatou , Allain Florence , Samaha Anne-Noël
Published: December 2021

Currently, there are no approved medications to treat cocaine addiction. In this context, d-amphetamine maintenance therapy is a promising pharmacological strategy to reduce cocaine use. In both male rats and human cocaine users, d-amphetamine treatment reduces cocaine taking and seeking. However, this has not been examined systematically in female animals, even though cocaine addiction afflicts both women and men, and the sexes can differ in their response to cocaine. Here, we determined how d-amphetamine maintenance therapy during cocaine self-administration influences cocaine use in female rats. In experiment 1, two groups of female rats received 14 intermittent access (IntA) cocaine self-administration sessions. One group received concomitant d-amphetamine maintenance treatment (COC + A rats; 5 mg/kg/day, via minipump), the other group did not (COC rats). After discontinuing d-amphetamine treatment, we measured responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed reinstatement of drug seeking. In experiment 2, we assessed the effects of d-amphetamine maintenance on these measures in already cocaine-experienced rats. To this end, rats first received 14 IntA cocaine self-administration sessions without d-amphetamine. They then received 14 more sessions now either with (COC/COC + A rats) or without (COC/COC rats) concomitant d-amphetamine treatment. In both experiments, d-amphetamine treatment did not influence cocaine-primed reinstatement of cocaine seeking. However, after d-amphetamine treatment, rats responded less for cocaine both under progressive ratio and extinction conditions. Thus, d-amphetamine treatment can both prevent and reverse increases in the motivation to take and seek cocaine in female animals.
Escape Steering by Cholecystokinin Peptidergic Signaling
Authors: Chen Lili , Liu Yuting , Su Pan , Hung Wesley , Li Haiwen , Wang Ya , Yue Zhongpu , Ge Minghai , Wu Zhengxing , Zhang Yan , Fei Peng , Chen Li-Ming , Tao Louis , Mao Heng , Zhen Mei , Gao Shangbang
Published: December 2021

Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that peptidergic signaling is an integral and necessary component of the Caenorhabditis elegans escape circuit. Combining genetic screening, electrophysiology and calcium imaging, we reveal that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega (Ω) turn, the last motor step where the animal robustly steers away from its original trajectory. We demonstrate in vivo and in vitro that CKR-1 is a Gαq protein coupled receptor for NLP-18. in vivo, NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18, removal of CKR-1, or specific knockdown of CKR-1 in SMD or AIB neurons lead to shallower turns hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)’s Ca2+ transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. in vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca2+ transients in SMD. Thus, cholecystokinin signaling modulates an escape circuit to generate robust escape steering.
Improved Transcriptome Assembly Using a Hybrid of Long and Short Reads with StringTie
Authors: Shumate Alaina , Wong Brandon , Pertea Geo , Pertea Mihaela
Published: December 2021

Short-read RNA sequencing and long-read RNA sequencing each have their strengths and weaknesses for transcriptome assembly. While short reads are highly accurate, they are unable to span multiple exons. Long-read technology can capture full-length transcripts, but its high error rate often leads to mis-identified splice sites, and its low throughput makes quantification difficult. Here we present a new release of StringTie that performs hybrid-read assembly. By taking advantage of the strengths of both long and short reads, hybrid-read assembly with StringTie is more accurate than long-read only or short-read only assembly, and on some datasets it can more than double the number of correctly assembled transcripts, while obtaining substantially higher precision than the long-read data assembly alone. Here we demonstrate the improved accuracy on simulated data and real data from Arabidopsis thaliana, Mus musculus, and human. We also show that hybrid-read assembly is more accurate than correcting long reads prior to assembly while also being substantially faster. StringTie is freely available as open source software at https://github.com/gpertea/stringtie.
Improving Lab Culture through Self-Assessment: A Case Study
Authors: Hernandez Soleil , Mumme Raymond , Court Laurence , Basha Daniel El , Gay Skylar , Marquez Barbara , Xiao Yao , Huang Kai , Baroudi Hana , Cao Wenhua , Cardenas Carlos , Douglas Raphael , Duryea Jack , Kaffey Zaphanlene , Mann Deborah , Nealon Kelly , Netheron Tucker , Nguyen Callistus , Oh Kyuhak , Olanrewaju Adenike , Sjogreen Carlos , Rhee DJ , Yang Jinzhong , Yu Cenji , Zhang Lifei , Zhao Yao , Ziyaee Hamid , Gronberg Mary
Published: December 2021

Purpose

Motivated by perceived dissatisfaction within our lab’s changed working environment brought about by the COVID-19 pandemic, we performed a self-assessment of our lab culture through anonymous surveys and live sessions.

Methods

In Survey 1, we asked each lab member to identify and rank up to 10 values that are important for a healthy lab environment. They were then asked to rate how well the lab embodied those values at two time points: before the COVID-19 pandemic while working onsite, and at the time of the survey while working remotely (10 months into the pandemic). In a series of live group sessions, we reviewed relevant literature and the survey results to finalize ten themes. We then reflected on each theme and proposed action items to address any deficiencies. Finally, we conducted Survey 2 after the self-assessment to judge the group’s finalized themes, implemented changes, and overall satisfaction with the assessment process.

Results

Themes identified were attitude, accountability, teamwork/collaboration, communication, diversity/inclusion, emotional intelligence, integrity, training, well-being, and adaptability in crisis-management. All lab members liked the self-assessment process and felt their voices were heard. On average, there was a 12% increase in satisfaction across all themes from the start to end of the lab assessment.

Conclusion

We successfully assessed the culture of our lab and subsequently improved lab member satisfaction. The success of this team project suggests that other scientific labs could benefit from similar interactive self-assessments.
HBV enveloped particle secretion is positively regulated by GRP78 through direct interaction with preS1
Authors: Shi Yueyuan , Jin Xin , Wu Shuang , Liu Junye , Zhang Hongpeng , Cai Xuefei , Yang Yuan , Zhang Xiang , Wei Jie , Peng Hui , Luo Miao , Zhou Hua , Zhou Huihao , Huang Ailong , Wang Deqiang
Published: December 2021

Hepatitis B virus (HBV) infection is a common cause of liver diseases worldwide. Existing drugs do not effectively eliminate HBV from infected hepatocytes; thus, novel curative therapies are needed. Enveloped-particle secretion is a key but poorly studied aspect of the viral life cycle. Here, we report that GRP78 positively regulates HBV enveloped-particle secretion. GRP78 is the specific target of preS1 binding; HBV can upregulate GRP78 in liver cell lines and sera from chronic hepatitis B patients. GRP78 promoted intact HBV-particle secretion in liver cell lines and an HBV transgenic-mouse model. Some peptides screened from preS1 via phage display could inhibit viral-particle secretion by interacting with GRP78 via hydrogen bonds and hydrophobic interactions, thereby disturbing the interaction with HBV particles. These results provide insight into enveloped-particle secretion in the HBV life cycle. GRP78 might be a potential target for HBV-infection treatment via restricting GRP78–preS1 interactions to block viral-particle secretion.

IMPORTANCE

HBV is a major human pathogen. The virus More than 250 million n individuals globally are chronically infected with HBV and can result in the infected personsabout 800,000 die for HBV-related disease annually. The mature HBV enveloped particles containing HBs and the relaxed circular (RC) DNA genome could secreted extracellularly as virions. And these enveloped virions serves as the infectious HBV particles for initiating a complete life cycle of the virus. Here, we show the GRP78 is the specific target of preS1 binding, and it could positive regulate HBV enveloped particle secretion in cell and HBV transgenic mice model. Furthermore, several peptides screened from preS1 and Phage screening could inhibit viral particle secretion by interacting with GRP78 and disturbing its interaction with HBV, and then block the life cycle of the virus. This has important implications for our understanding of the mechanisms of antivirals that target intact HBV particles secretion.
Effect of growth forms of bamboo on the mycorrhizal and fluorescent pseudomonas population
Authors: Das Solomon , Singh Y. P. , Negi Yogesh K. , Shrivastav P. C.
Published: December 2021

Bamboo, also called as the poor man’s timber, is one of the fastest growing giant grass species. Having shallow root system and fast growth rate, the dependability of the plant on the rhizospheric microbial web cannot be denied. The study was conducted to explore the population and seasonal variations of indigenous mycorrhizal fungi as well as the functional diversity of plant growth promoting bacteria, especially fluorescent pseudomonas from the different growth forms of Dendrocalamus strictus, the most commonly present bamboo species in Indian sub-continent. In a past study, it was established that the growth forms of D. strictus which developed over time in their respective locations, were genetically varied. The present research further explores the variations in their respective rhizospheric microbes and looks for the role of plant selection phenomenon. Considerable variation in mycorrhizal structures and in the functional diversity of fluorescent pseudomonas was registered. It seems probable that selection pressure of nutrient deficient condition has created a condition that promoted occurrence of high numbers of P solubilisers which, in turn, boosted the mycorrhizal as well as bamboo growth.