bluuebunny/crossref_metadata_2025 huggingface dataset:
Paths to Oblivion: Common Neural Mechanisms of Anaesthesia and Disorders of Consciousness
Authors: Luppi Andrea I. , Mediano Pedro A.M. , Rosas Fernando E. , Allanson Judith , Pickard John D. , Williams Guy B. , Craig Michael M , Finoia Paola , Peattie Alexander R.D. , Coppola Peter , Owen Adrian , Naci Lorina , Menon David K. , Bor Daniel , Stamatakis Emmanuel A.
Published: February 2021

The human brain generates a rich repertoire of spatiotemporal dynamics during normal wakefulness, supporting a wide variety of conscious experiences and cognitive functions. However, neural dynamics are reconfigured, in comparable ways, when consciousness is lost either due to anaesthesia or disorders of consciousness (DOC). Here, leveraging a neurobiologically realistic whole-brain computational model informed by functional MRI, diffusion MRI, and PET, we sought to identify the neurobiological mechanisms that explain the common reconfiguration of neural dynamics observed both for transient pharmacological intervention and chronic neuroanatomical injury. Our results show that, by incorporating local inhibitory action through a PET-based GABA receptor density map, our model can reproduce the brain dynamics of subjects undergoing propofol anaesthesia, and that this effect depends specifically on the spatial distribution of GABA receptors across cortical regions. Additionally, using a structural connectome obtained from DOC patients, we demonstrate how the dynamics that characterise loss of consciousness can emerge from changes in neuroanatomical connectivity. Crucially, we find that each of these two interventions generalises across datasets: a model with increased GABA-mediated inhibition can reproduce the dynamics of DOC patients’ brains, and a model with a DOC connectome is also compatible with brain dynamics observed during propofol anaesthesia. These results demonstrate how increased inhibition and connectome randomisation represent different neurobiological paths towards the characteristic dynamics of the unconscious brain. Overall, the present findings begin to disentangle the neurobiological mechanisms by which highly dissimilar perturbations of the brain’s neurodynamics can lead to unconsciousness.
Adenylnucleotide-mediated binding of the PII-like protein SbtB contributes to controlling activity of the cyanobacterial bicarbonate transporter SbtA
Authors: Förster Britta , Mukherjee Bratati , Rourke Loraine M. , Kaczmarski Joe A. , Jackson Colin J. , Price G. Dean
Published: February 2021

Cyanobacteria have evolved a remarkably powerful CO2concentrating mechanism (CCM), enabling high photosynthetic rates in environments with limited inorganic carbon (Ci). Therefore, this CCM is a promising system for integration into higher plant chloroplasts to boost photosynthetic efficiency and yield. The CCM depends on active Ci uptake, facilitated by bicarbonate transporters and CO2pumps, to elevate CO2concentration around the active sites of the primary CO2fixing enzyme, Rubisco, which is encapsulated in cytoplasmic micro-compartments (carboxysomes). The essential CCM proteins have been identified, but the molecular signals and regulators that coordinate function in response to light, Ci availability and other environmental cues are largely unknown. Here, we provide evidence, based on a novelin vitrobinding system, for a role of the PII-like SbtB protein in regulating Ci uptake by the bicarbonate transporter, SbtA, in response to the cellular adenylate energy charge (AEC) through dynamic protein-protein interaction. Binding of the SbtA and SbtB proteins from two phylogenetically distant species,Cyanobium sp. PCC7001 andSynechococcus elongatusPCC7942, was inhibited by high ATP, and promoted by low [ATP]:[ADP or AMP] ratiosin vitro, consistent with a sensory response to the AEC mediated through adenylnucleotide ligand-specific conformation changes in SbtB.In vivo, cell cultures of S. elongatus showed up to 70% SbtB-dependent down-regulation of SbtA bicarbonate uptake activity specifically in the light activation phase during transitions from dark to low light when low cellular AEC is expected to limit metabolic activity. This suggests SbtB may function as a curfew protein during prolonged low cellular AEC and photosynthetically unfavourable conditions to prevent energetically futile and physiologically disadvantageous activation of SbtA.
Prostate cancer screening in hospitalized patients: Results from the Nationwide Inpatient Sample
Authors: Irfan Furqan B. , Ahmed Fahad Shabbir , Masucci Monica V. , Cerimele Angelina A. , Nguyen Thu , Sharrak Aryana , Nguyen David M , Tariq Tooba , Baydoun Hussein , Hasan Ahmad , Awad Mohamed E , Saleh Khaled , Karabon Patrick
Published: February 2021

Background

Prostate cancer (PCa) is the most common non-skin cancer in American men. The aim of the study was to determine the nationwide prevalence, trends, and predictors of inpatient PCa screening encounters in patients with average risk of PCa using the National Inpatient Sample (NIS) database.

Methods

The NIS database from 2006 to 2014 was used to evaluate PCa screening among hospitalized patients in the United States (US). All hospitalized male patients between the ages of 45 and 69 at average risk for PCa were included. The outcome was whether a patient had an encounter for prostate cancer as noted on their discharge record. Variables analyzed included demographic factors, hospital characteristics, and other concomitant diagnoses for prostate or male urinary problems.

Results

The prevalence of inpatient PCa screening was 2.57 per 100,000 hospital discharges. In a multivariate setting, the following were significant factors associated with greater odds of inpatient PCa screening: Medicare (AOR: 3.07; P = 0.0016), Self-Pay or Uninsured patients (AOR: 1.74; P = 0.0371), rural (AOR: 11.9; P = < 0.0001) or urban nonteaching hospitals (AOR: 5.26; P = < 0.0001), receiving care in the Midwest (AOR: 4.90; P = < 0.0001), a diagnosis for urinary tract infections (P = 0.0367), genitourinary symptoms (P < 0.0001), hyperplasia of prostate (P = 0.0006), or other male genital disorder (P < 0.0001).

Conclusion

According to current cancer screening guidelines, PSA screening should include shared decision making between physicians and patients. In light of unequal access to quality healthcare, there exist disparities in uninsured and rural patients for cancer screening. Screening tools such as prostate specific antigen (PSA) are minimally invasive modalities in the inpatient setting that can help screen individuals at increased risk for the development of prostate cancer, allowing for early detection, prevention, improved rates of cure and ultimately, decreased rates of mortality.
ToxCast chemical library screen identifies diethanolamine as an activator of Wnt signaling
Authors: Wolter Justin M. , Jimenez Jessica A. , Stein Jason L. , Zylka Mark J.
Published: February 2021

Numerous autism spectrum disorder (ASD) risk genes are associated with Wnt signaling, suggesting that brain development may be especially sensitive to genetic perturbation of this pathway. Additionally, valproic acid, which modulates Wnt signaling, increases risk for ASD when taken during pregnancy. We previously found that an autism-linked gain-of-function UBE3AT485Amutant construct hyperactivated canonical Wnt signaling, providing a genetic means to elevate Wnt signaling above baseline levels. To identify environmental use chemicals that enhance or suppress Wnt signaling, we screened the ToxCast Phase I and II libraries in cells expressing this autism linkedUBE3AT485gain-of-function mutant construct. Using structural comparisons, we identify classes of chemicals that stimulated Wnt signaling, including ethanolamines, as well as chemicals that inhibited Wnt signaling, such as agricultural pesticides, and synthetic hormone analogs. To prioritize chemicals for follow-up, we leveraged predicted human exposure data, and identified diethanolamine (DEA) as a chemical that both stimulates Wnt signaling inUBE3AT485A–transfected cells and has a high potential for prenatal exposure in humans. DEA also enhanced proliferation in two primary human neural progenitor cell lines. Overall, this study identifies chemicals with the potential for human exposure that influence Wnt signaling in human cells.
Magnetically stimulated cryogels to enhance osteogenic and chondrogenic differentiation of stem cells
Authors: Odabas Sedat , Tevlek Atakan , Erenay Berkay , Aydın Halil Murat , Süloglu Aysun Kılıç , Saglam Atiye Seda Yar , Garipcan Bora
Published: February 2021

Cells can respond to the physical stimulus that comes from their micro-environments. There are several strategies to alter cell behavior. Several tissues like bone and cartilage, which are the point of interest of regenerative medicine, are under significant degrees of mechanical stress in real life. Within this stress, the arising mechanotransduction effect may trigger several behavioral responses on cells. As a novel and efficient way, magnetic nanoparticles can be used to make such a mechanotransductive effect on cells.

In this study, pre-functionalized Fe3O4superparamagnetic magnetite nanoparticles were synthesized and used to fabricate gelatin-based magnetic cryogels. Cell growth, tissue-specific metabolic activities, differentiation potential to the bone, and cartilage under static magnetic field at different magnetic field strength (1000-4000G) were investigated. Results indicated that there was a better induction in considerable higher magnetic field among all others and magnetic cryogels helps to mediate mesenchymal stem cell behaviour, promote their growth and induce osteogenic and chondrogenic differentiation.
PandoraGAN: Generating antiviral peptides using Generative Adversarial Network
Authors: Surana Shraddha , Arora Pooja , Singh Divye , Sahasrabuddhe Deepti , Valadi Jayaraman
Published: February 2021

The continuous increase in pathogenic viruses and the intensive laboratory research emphasizes the need for cost and time efficient drug development. This accelerates research for alternate drug candidates like antiviral peptides(AVP) that have therapeutic and prophylactic potential and gaining attention in recent times. However, diversity in their sequences, limited and non-uniform characterization often limit their applications. Isolating newer peptide backbones with required characteristics is a cumbersome process with many design-test-build cycles. Advanced deep learning approaches such as generative adversarial networks (GAN) can be helpful to expedite the initial stage of developing novel peptide drugs. In this study, we developed PandoraGAN that uses a manually curated training dataset of 130 highly active peptides that includes peptides from known databases (such as AVPdb) and literature to generate novel antiviral peptides. The underlying architecture in PandoraGAN is able to learn a good representation of the implicit properties of antiviral peptides. The generated sequences from PandoraGAN are validated based on physico-chemical properties. They are also compared with the training dataset statistically using Pearson’s correlation and Mann-Whitney U-test. We therefore confirm that PandoraGAN is capable of generating a novel antiviral peptide backbone showing similar properties to that of the known highly active antiviral peptides. This approach exhibits a potential to discover novel patterns of AVP which may have not been seen earlier with traditional methods. To our knowledge this is the first ever use of GAN models for antiviral peptides across the viral spectrum.
Changes of mind after movement onset: a motor-state dependent decision-making process
Authors: Cos Ignasi , Pezzulo Giovanni , Cisek Paul
Published: February 2021

Decision-making is traditionally described as a cognitive process of deliberation followed by commitment to an action choice, preceding the planning and execution of the chosen action. However, this is challenged by recent data suggesting that multiple options are specified simultaneously and compete in pre-motor cortical areas for selection and execution. Previous studies focused on the competition during planning, and leave unaddressed the dynamics of decisions during movement. Does deliberation extend into the execution phase? Are non-selected options still considered? Here we studied a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a rectangular target, where reward was distributed non-uniformly at the target. Critically, we applied mechanical perturbations to the arm during movement to study under which conditions such perturbations produce changes of mind. Our results show that participants initially selected the direction of movement towards the highest reward region, and changed their mind most frequently when the two choices offered the same reward, showing that deliberation continues and follows cost-benefit considerations during movement. Furthermore, changes of mind were dependent upon the intensity of the perturbation and the current state of the motor system, including velocity and distance to targets. Although reward remains most relevant, our results indicate that the state of the motor system when the perturbation occurs is a crucial determinant of changes of mind. This indicates that the neural circuits that assess reward and those that control movements operate synergistically rather than sequentially during decision-making.

Significance Statement

Our study provides supporting evidence for the notion that deliberation during decision-making continues after movement onset because unselected potential actions are not completely suppressed or discarded. From a neurophysiological perspective, our findings suggest that the competition between actions is not over before action initiation, possibly because the initially unselected neuronal population retains some sub-threshold activation, which enables them to take control afterwards. Furthermore, our findings also suggest that decision-makers have a variable degree of commitment to their initial choice, which depends on the relative reward of the offers and on the state of the motor system. The commitment is stronger if the initially selected plan leads to higher rewards, and changes of mind occur more frequently if the velocity and relative position of the end-point are within specific ranges.
Primary motor cortex activity traces distinct trajectories of population dynamics during spontaneous facial motor sequences in mice
Authors: Boffi Juan Carlos , Wiessalla Tristan , Prevedel Robert
Published: February 2021

We explore the link between on-going neuronal activity at primary motor cortex (M1) and face movement in awake mice. By combining custom-made behavioral sequencing analysis and fast volumetric Ca2+-imaging, we simultaneously tracked M1 population activity during many different facial motor sequences. We show that a facial area of M1 displays distinct trajectories of neuronal population dynamics across different spontaneous facial motor sequences, suggesting an underlying population dynamics code.

Significance statement

How our brain controls a seemingly limitless diversity of body movements remains largely unknown. Recent research brings new light into this subject by showing that neuronal populations at the primary motor cortex display different dynamics during forelimb reaching movements versus grasping, which suggests that different motor sequences could be associated with distinct motor cortex population dynamics. To explore this possibility, we designed an experimental paradigm for simultaneously tracking the activity of neuronal populations in motor cortex across many different motor sequences. Our results support the concept that distinct population dynamics encode different motor sequences, bringing new insight into the role of motor cortex in sculpting behavior while opening new avenues for future research.
High-pressure sprayed siRNAs influence the efficiency but not the profile of transitive silencing
Authors: Uslu Veli Vural , Dalakouras Athanasios , Steffens Victor A , Krczal Gabi , Wassenegger Michael
Published: February 2021

In plants, small interfering RNAs (siRNAs) are a quintessential class of RNA interference (RNAi)-inducing molecules produced by the endonucleolytic cleavage of double stranded RNAs (dsRNAs). In order to ensure robust RNAi, siRNAs are amplified through a positive feedback mechanism called transitivity. Transitivity relies on RNA-DIRECTED-RNA POLYMERASE 6 (RDR6)-mediated dsRNA synthesis using siRNA-targeted RNA. The newly synthesized dsRNA is subsequently cleaved into secondary siRNAs by DICER-LIKE (DCL) endonucleases. Just like primary siRNAs, secondary siRNAs are also loaded into ARGONAUTE proteins (AGOs) to form an RNA-induced silencing complex (RISC) reinforcing the cleavage of the target RNA. Although the molecular players underlying transitivity are well established, the mode of action of transitivity remains elusive. In this study, we investigated the influence of primary target sites on transgene silencing and transitivity using the GFP-expressingNicotiana benthamiana16C line, high pressure spraying protocol (HPSP), and synthetic 22-nucleotide (nt) long siRNAs. We found that the 22-nt siRNA targeting the 3’ of the GFP transgene was less efficient in inducing silencing when compared to the siRNAs targeting the 5’ and middle region of the GFP. Moreover, sRNA sequencing of locally silenced leaves showed that the amount but not the profile of secondary RNAs is shaped by the occupancy of the primary siRNA triggers on the target RNA. Our findings suggest that RDR6-mediated dsRNA synthesis is not primed by primary siRNAs and that dsRNA synthesis appears to be generally initiated at the 3’ end of the target RNA.

SIGNIFICANCE STATEMENT

This work answers a long-standing question about the role of siRNA triggers in initiating transitive silencing. By using high-pressure spraying-mediated delivery of synthetic siRNAs, we provided experimental evidence that target position of 22-nt-long primary siRNAs influences the efficiency of RDR6-driven double stranded RNA (dsRNA) synthesis, but it does not change the profile of accumulating secondary siRNAs originating from processing of RDR6-produced dsRNA.
On the phenology of protists: Recurrent patterns reveal seasonal variation of protistan (Rhizaria: Cercozoa, Endomyxa) communities in tree canopies
Authors: Walden Susanne , Jauss Robin-Tobias , Feng Kai , Fiore-Donno Anna Maria , Dumack Kenneth , Schaffer Stefan , Wolf Ronny , Schlegel Martin , Bonkowski Michael
Published: February 2021

Tree canopies are colonized by billions of highly specialized microorganisms that are well adapted to the extreme microclimatic conditions, caused by diurnal fluctuations and seasonal changes. In this study we investigated seasonality patterns of protists in tree canopies of a temperate floodplain forest via high-throughput sequencing with group-specific primers for the phyla Cercozoa and Endomyxa. We observed consistent seasonality and identified divergent spring and autumn taxa. Tree crowns were characterized by a dominance of bacterivores and omnivores, while eukaryvores gained a distinctly larger share in litter and soil communities on the ground. Seasonality was largest among communities detected on the foliar surface. Higher variance within alpha diversity of foliar communities in spring indicated greater heterogeneity during community assembly. However, communities underwent distinct changes during the aging of leaves in autumn, reflecting recurring phenological changes during microbial colonization of leaves. Surprisingly, endomyxan root pathogens appeared to be exceptionally abundant across tree canopies during autumn season, demonstrating a potential role of the canopy surface as an important reservoir for wind-dispersed propagules. Overall, about 80% of detected OTUs could not be assigned to known species – representing only a fraction of dozens of microeukaryotic taxa whose canopy inhabitants are waiting to be discovered.
Simulating the emergence of the Visual Word Form Area: Recycling a convolutional neural network for reading
Authors: Hannagan T. , Agrawal A. , Cohen L. , Dehaene S.
Published: February 2021

The visual word form area (VWFA) is a region of human inferotemporal cortex that emerges at a fixed location in occipitotemporal cortex during reading acquisition, and systematically responds to written words in literate individuals. According to the neuronal recycling hypothesis, this region arises through the repurposing, for letter recognition, of a subpart of the ventral visual pathway initially involved in face and object recognition. Furthermore, according to the biased connectivity hypothesis, its universal localization is due to pre-existing connections from this subregion to areas involved in spoken language processing. Here, we evaluate those hypotheses in an explicit computational model. We trained a deep convolutional neural network of the ventral visual pathway, first to categorize pictures, and then to recognize written words invariantly for case, font and size. We show that the model can account for many properties of the VWFA, particularly when a subset of units possesses a biased connectivity to word output units. The network develops a sparse, invariant representation of written words, based on a restricted set of reading-selective units. Their activation mimics several properties of the VWFA, and their lesioning causes a reading-specific deficit. Our simulation fleshes out the neuronal recycling hypothesis, and make several testable predictions concerning the neural code for written words.
A deep learning model for fish classification base on DNA barcode
Authors: Jin Lina , Yu Jiong , Yuan Xiaoqian , Du Xusheng
Published: February 2021

Fish is one of the most extensive distributed organisms in the world, fish taxonomy is an important part of biodiversity and is also the basis of fishery resources management. However, the morphological characters are so subtle to identify and intact specimens are not available sometimes, making the research and application of morphological method laborious and time-consuming. DNA barcoding based on a fragment of the cytochrome c oxidase subunit I (COI) gene is a valuable molecular tool for species identification and biodiversity studies. In this paper, a novel deep learning classification approach that fuses Elastic Net-Stacked Autoencoder (EN-SAE) with Kernel Density Estimation (KDE), named ESK-model, is proposed bases on DNA barcode. In stage one, ESK-model preprocesses the original data from COI fragments. In stage two, EN-SAE is used to learn the deep features and obtain the outgroup score of each fish. In stage three, KDE is used to select the threshold base on the outgroup scores and classify fish from different families. The effectiveness and superiority of ESK-model have been validated by experiment on three dominant fish families and comparisons with state-of-the-art methods. Those findings confirm that the ESK-model can accurately classify fish from different family base on DNA barcode.
Comparative genome analysis revealed gene inversions, boundary expansion and contraction, and gene loss inStemona sessilifolia(Miq.) Miq. chloroplast genome
Authors: Liu Jingting , Jiang Mei , Chen Haimei , Liu Yu , Liu Chang , Wu Wuwei
Published: February 2021

Stemona sessilifolia(Miq.) Miq., commonly known as Baibu, is one of the most popular herbal medicines in Asia. In Chinese Pharmacopoeia, Baibu has multiple authentic sources, and there are many homonym herbs sold as Baibu in the herbal medicine market. The existence of the counterfeits of Baibu brings challenges to its identification. To assist the accurate identification of Baibu, we sequenced and analyzed the complete chloroplast genome ofStemona sessilifoliausing next-generation sequencing technology. The genome was 154,039 bp in length, possessing a typical quadripartite structure consisting of a pair of inverted repeats (IRs: 27,094 bp) separating by a large single copy (LSC: 81,950 bp) and a small single copy (SSC: 17,901 bp). A total of 112 unique genes were identified, including 80 protein-coding, 28 transfer RNA, and four ribosomal RNA genes. Besides, 45 tandem, 27 forward, 23 palindromic, and 72 simple sequence repeats were detected in the genome by repeat analysis. Compared with its counterfeits(Asparagus officinalisandCarludovica palmate), we found that IR expansion and SSC contraction events ofStemona sessilifoliaresulted in two copies ofthe rpl22gene in the IR regions and partial duplication of thendhFgene in the SSC region. Secondly, an approximately 3-kb-long inversion was identified in the LSC region, leading tothe petAandcemAgene presented in the complementary strand of the chloroplast DNA molecule. Comparative analysis revealed some highly variable regions, includingtrnF-GAA_ndhJ, atpB_rbcL, rps15_ycf1, trnG-UCC_trnR-UCU, ndhF_rpl32.Finally, gene loss events were investigated in the context of phylogenetic relationships. In summary, the complete plastome ofStemona sessilifoliawill provide valuable information for the molecular identification of Baibu and assist in elucidating the evolution ofStemona sessilifolia.
Saccharomyces cerevisiaedeficient in the early anaphase release of Cdc14 can traverse anaphase I without ribosomal DNA disjunction and successfully complete meiosis
Authors: Yellman Christopher M.
Published: February 2021

Eukaryotic meiosis is a specialized cell cycle involving two successive nuclear divisions that lead to the formation of haploid gametes. The phosphatase Cdc14 plays an essential role in meiosis as revealed in studies of the yeastSaccharomyces cerevisiae. Cdc14 is stored in the nucleolus, a sub-nuclear domain containing the ribosomal DNA, and its release is regulated by two distinct pathways, one acting in early anaphase I of meiosis and a second at the exit from meiosis II. The early anaphase release is thought to be important for disjunction of the ribosomal DNA, disassembly of the anaphase I spindle, spindle pole re-duplication and the counteraction of CDK, all of which are required for progression into meiosis II. The release of Cdc14 from its nucleolar binding partner Net1 is stimulated by phosphorylation of cyclin-dependent kinase sites in Net1, but the importance of that phospho-regulation in meiosis is not well understood. We inducednet1-6cdkmutant cells to enter meiosis and examined the localization of Cdc14 and various indicators of meiotic progression. Thenet1-6cdkmutations inhibit, but don’t fully prevent Cdc14 release, and they almost completely prevent disjunction of the ribosomal DNA during meiosis I. Failure to disjoin the ribosomal DNA is lethal in mitosis, and we expected the same to be true in meiosis. However, the cells were able to complete meiosis II, yielding the expected four meiotic products as viable spores. Therefore, all ribosomal DNA disjunction required for meiosis can occur in meiosis II. We discuss the implications of these findings for our understanding of meiotic chromosome segregation.
The shifting of dominating roles between structural cells and immune cells are key regulators of human adipose tissues aging
Authors: Zhou Wenyan , Lin Junxin , Hu Xueqing , Yao Xudong , Ouyang Hongwei
Published: February 2021

Adipose tissue is a highly dynamic organ with complex cellular composition. Aging induces adipose tissue function decline and relocation of peripheral adipose tissue to abdominal compartment, which often associated with inflammation and metabolic disorders. Here we performed single-cell RNA sequencing to comprehensively and unbiasedly deconvolve how subcutaneous adipose tissue (SAT) responses to aging. We collected >25,000 stromal vascular cells from abdominal and gluteofemoral SAT of young and old donors. Analyses of transcription signatures and cell networks uncovered impaired adipogenesis and extracellular matrix synthesis capacity of APC, altered metabolic phenotype of immune cells and shifted tissue-dominating cells that can be used to predict adipose tissue aging. We also reported aging-associated distinct transcriptional program between gluteofemoral SAT and abdominal SAT. Our work thus reveals unanticipated cellular, immunological, metabolic and site-specific aspects of human adipose tissues aging process, providing valuable resource for better understanding of aging-associated adipose tissue dysfunction.
The dynamic transition of persistence towards the VBNC state during stationary phase is driven by protein aggregation
Authors: Dewachter Liselot , Bollen Celien , Wilmaerts Dorien , Louwagie Elen , Herpels Pauline , Matthay Paul , Khodaparast Ladan , Khodaparast Laleh , Rousseau Frederic , Schymkowitz Joost , Michiels Jan
Published: February 2021

Decades of research into bacterial persistence has been unable to fully characterize this antibiotic-tolerant phenotype, thereby hampering the development of therapies effective against chronic infections. Although some active persister mechanisms have been identified, the prevailing view is that cells become persistent because they enter a dormant state. We therefore characterized starvation-induced dormancy inEscherichia coli. Our findings indicate that dormancy develops gradually; persistence strongly increases during stationary phase and decreases again as persisters enter the viable but nonculturable (VBNC) state. Importantly, we show that dormancy development is tightly associated with progressive protein aggregation, which occurs concomitantly with ATP depletion during starvation. Persisters contain protein aggregates in an early developmental stage while VBNC cells carry more mature aggregates. Finally, we show that at least one persister protein, ObgE, works by triggering aggregation and thereby changing the dynamics of persistence and dormancy development. These findings provide evidence for a genetically-controlled, gradual development of persisters and VBNC cells through protein aggregation.
Optimal Reinforcement Learning with Asymmetric Updating in Volatile Environments: a Simulation Study
Authors: Kandroodi Mojtaba Rostami , Vahabie Abdol-Hossein , Ahmadi Sara , Araabi Babak Nadjar , Ahmadabadi Majid Nili
Published: February 2021

Abstract

The ability to predict the future is essential for decision-making and interaction with the environment to avoid punishment and gain reward. Reinforcement learning algorithms provide a normative way for interactive learning, especially in volatile environments. The optimal strategy for the classic reinforcement learning model is to increase the learning rate as volatility increases. Inspired by optimistic bias in humans, an alternative reinforcement learning model has been developed by adding a punishment learning rate to the classic reinforcement learning model. In this study, we aim to 1) compare the performance of these two models in interaction with different environments, and 2) find optimal parameters for the models. Our simulations indicate that having two different learning rates for rewards and punishments increases performance in a volatile environment. Investigation of the optimal parameters shows that in almost all environments, having a higher reward learning rate compared to the punishment learning rate is beneficial for achieving higher performance which in this case is the accumulation of more rewards. Our results suggest that to achieve high performance, we need a shorter memory window for recent rewards and a longer memory window for punishments. This is consistent with optimistic bias in human behavior.
Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration
Authors: Yu Ling-Yea , Tseng Ting-Jen , Lin Hsuan-Chao , Lu Ting-Xuan , Tsai Chia-Jung , Lin Yu-Chiao , Hsu Chi-Lin , Tsai Feng-Chiao
Published: February 2021

Integrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a “two-hit” screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced translocation of yes-associated protein (YAP) into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Altogether, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration, and introduced “synthetic dysmobility” as a novel strategy to collaboratively control cell migration.

One Sentence Summary

Blocking collaborative pathways within the integrated signaling network synergistically disrupts the migration of cells.
A practical modification to a resting state fMRI protocol for improved characterization of cerebrovascular function
Authors: Stickland Rachael C. , Zvolanek Kristina M. , Moia Stefano , Ayyagari Apoorva , Caballero-Gaudes César , Bright Molly G.
Published: February 2021

Cerebrovascular reactivity (CVR), defined here as the Blood Oxygenation Level Dependent (BOLD) response to a CO2pressure change, is a useful metric of cerebrovascular function. Both the amplitude and the timing (hemodynamic lag) of the CVR response can bring insight into the nature of a cerebrovascular pathology and aid in understanding noise confounds when using functional Magnetic Resonance Imaging (fMRI) to study neural activity. This research assessed a practical modification to a typical resting-state fMRI protocol, to improve the characterization of cerebrovascular function. In 9 healthy subjects, we modelled CVR and lag in three resting-state data segments, and in data segments which added a 2–3 minute breathing task to the start of a resting-state segment. Two different breathing tasks were used to induce fluctuations in arterial CO2pressure: a breath-hold task to induce hypercapnia (CO2increase) and a cued deep breathing task to induce hypocapnia (CO2decrease). Our analysis produced voxel-wise estimates of the amplitude (CVR) and timing (lag) of the BOLD-fMRI response to CO2by systematically shifting the CO2regressor in time to optimize the model fit. This optimization inherently increases grey matter CVR values and fit statistics. The inclusion of a simple breathing task, compared to a resting-state scan only, increases the number of voxels in the brain that have a significant relationship between CO2and BOLD-fMRI signals, and improves our confidence in the plausibility of voxel-wise CVR and hemodynamic lag estimates. We demonstrate the clinical utility and feasibility of this protocol in an incidental finding of Moyamoya disease, and explore the possibilities and challenges of using this protocol in younger populations. This hybrid protocol has direct applications for CVR mapping in both research and clinical settings and wider applications for fMRI denoising and interpretation.
Improving range shift predictions: enhancing the power of traits
Authors: Cannistra Anthony F. , Buckley Lauren B.
Published: February 2021

Accurately predicting species’ range shifts in response to environmental change is a central ecological objective and applied imperative. In synthetic analyses, traits emerge as significant but weak predictors of species’ range shifts across recent climate change. These studies assume linearity in the relationship between a trait and its function, while detailed empirical work often reveals unimodal relationships, thresholds, and other nonlinearities in many trait-function relationships. We hypothesize that the use of linear modeling approaches fails to capture these nonlinearities and therefore may be under-powering traits to predict range shifts. We evaluate the predictive performance of four different machine learning approaches that can capture nonlinear relationships (ridge-regularized linear regression, ridge-regularized kernel regression, support vector regression, and random forests). We validate our models using four multi-decadal range shift datasets in montane plants, montane small mammals, and marine fish. We show that nonlinear approaches perform substantially better than least-squares linear modeling in reproducing historical range shifts. In addition, using novel model observation and interrogation techniques, the trait classes (e.g. dispersal-or diet-related traits) that we identify as primary drivers of model predictions are consistent with expectations. However, disagreements among models in the directionality of trait predictors suggests limits to trait-based statistical predictive frameworks.
Spatial model of water quality in Southeast Asian urban lake based on HBI using macrozoobenthos diversity as a proxy
Authors: Wibowo Andri
Published: February 2021

Urban lake is one of ecosystem that has experienced anthropogenic pressures and this can affect its water quality. One of a robust approach to assess the water quality is by using Hilsenhoff Biotic Index (HBI). This tool is quite versatile since it can be applied by using any aquatic organism as proxy including macrozoobenthos. This invertebrate group also has an advantage since it is common and easy to collect. Here this study is first, aiming to provide HBI based water quality spatial model using macrozoobenthos as a proxy applied in urban lake in West Java in Southeast Asia and second to seek the best model that can represent the water quality variables in particular dissolved oxygen (DO), pH, and temperature. Based on the spatial model and HBI, either inlet or outlet parts of the lake, it has better water quality in comparison to central parts. Based on HBI values, water quality in inlet and outlet parts (HBI = 6.7) is categorized as fair and poor (HBI = 6.9) for the central parts of the lake. The increase in HBI and decrease in water quality are positively correlated with the increase in water temperature variable in comparison to water DO and pH variables. Akaike model selection confirms that the macrozoobenthos diversity can be used as a proxy for increase in water temperature (Ψ)HBI(~temp)(AIC = −10.264) followed by combination of water temperature increase and decrease in DO(Ψ)HBI(~temp+DO)(AIC = −9.042398).
Better later: evening practice is advantageous for motor skill consolidation in the elderly
Authors: Korman Maria , Gal Carmit , Gabitov Ella , Karni Avi
Published: February 2021

How does the time of day of a practice session affect learning of a new motor sequence in the elderly? Participants practiced a given finger tapping sequence either during morning or evening hours. All participants robustly improved performance speed within the session concurrent with a reorganization of the tapping pattern of the sequence. However, evening-trained participants showed additional gains overnight and at 1 wk posttraining; moreover, evening training led to a further reorganization of the tapping pattern offline. A learning experience preceding nocturnal sleep can lead to a task-specific movement routine as an expression of novel “how to” knowledge in the elderly.
Structural and theoretical analysis of 2-chloro-4-nitroaniline and 2-methyl-6-nitroaniline salts
Authors: Medviediev Volodymyr , Daszkiewicz Marek
Published: February 2021

The crystal structures of five new salts of 2-chloro-4-nitroaniline (2Cl4na) and 2-methyl-6-nitroaniline (2m6na) with inorganic acids, namely, 2-chloro-4-nitroanilinium bromide, C6H6ClN2O2
+·Br− (1), 2-chloro-4-nitroanilinium hydrogen sulfate, C6H6ClN2O2
+·HSO4
− (2), 2-methyl-6-nitroanilinium bromide, C7H9N2O2
+·Br− (3), 2-methyl-6-nitroanilinium triiodide, C7H9N2O2
+·I3
− (4), and 2-methyl-6-nitroanilinium hydrogen sulfate, C7H9N2O2
+·HSO4
− (5), were determined by single-crystal X-ray diffraction. Theoretical calculations of the relaxed potential energy surface (rPES) revealed that the energy barriers for the rotation of the nitro group for isolated H2Cl4na+ and H2m6na+ cations are 4.6 and 11.6 kcal mol−1, respectively. The ammonium group and respective anions form hydrogen bonds which are the most important interactions and are arranged in zero- (in 3), one- (in 1 and 4) or two-dimensional (in 2 and 5) networks. Hydrogen-bonding patterns were analyzed by means of mathematical relationships between graph-set descriptors and compared with previously reported nitroaniline salts. Hirshfeld surface analysis indicates that the nitro group plays a dominant role among the weak interactions, i.e. C—H...O(NO2), NO2...π(Ar) and O(NO2)...π(NO2). The frequency of the νsNO2 vibration is correlated with the type of interaction in which the NO2 group is involved. Analysis of the νsNO2 band observed in the IR and Raman spectra allowed an assessment of its shift in the sequence (H2m6na)I3 (4) < (H2m6na)HSO4 (5) < (H2m6na)Br (3) < (H2Cl4na)Br (1) < (H2Cl4na)HSO4 (2).
Attenuation and dispersion phenomena of shear waves in anelastic and elastic porous strips
Authors: Alam Parvez , Jena Suprava , Badruddin Irfan Anjum , Khan Tatagar Mohammad Yunus , Kamangar Sarfaraz
Published: February 2021

Purpose

This paper aims to study the attenuation and dispersion phenomena of shear waves in anelastic and elastic porous strips. Numerical investigations are performed for the phase and damped velocity profiles of the wave. For numerical computation purposes, water-saturated limestone and kerosene oil saturated sandstone for the first and second porous strips, respectively. Some other peculiarities have been observed and discussed.

Design/methodology/approach

Dispersion and attenuation characteristic of the shear wave propagations have been studied in an inhomogeneous poro-anelastic strip of finite thickness, which is clamped between an inhomogeneous poroelastic strip of finite thickness and an elastic half-space. Both the strips are initially stressed and the half-space is self-weighted. Analytical methods are used to calculate the interior deformations of the model with the involvement of special functions. The determination of the frequency equation, which includes the Bessel’s and Whittaker functions, has been obtained using the prescribed boundary conditions.

Findings

Impacts of attenuation coefficient, dissipation factor, inhomogeneities, initial stresses, Biot’s gravity, porosity and thickness ratio parameters on the velocity profile of the wave have been demonstrated through the graphical visuals. These parameters are playing an important role and working as a catalyst in affecting the propagation behaviour of the wave.

Originality/value

Inclusion of the concept of doubly layered initially stressed inhomogeneous porous structure of elastic and anelastic medium bedded over a self-weighted half-space medium brings a novelty to the existing literature related to the study of shear wave. It may be helpful to geologists, seismologists and structural engineers in the development of theoretical and practical studies.
Capitalizing on the spirit of giving: seeding virtual gift purchases in online social networks
Authors: Song Reo , Moisio Risto , Kang Moon Young
Published: February 2021

Purpose

Virtual gifts have emerged as a common feature of online communities, social gaming and social networks. This paper aims to examine how network-related variables and gift-seeding impact virtual gift sales. The network variables include gift-giver centrality and gift-giving dispersion, capturing, respectively, the relative importance of gift-givers in a network and their tendency to give gifts to a greater or lesser number of network peers. Gift-seeding tactics capture social network firms’ attempts to stimulate virtual gift purchases by awarding virtual gifts to network members.

Design/methodology/approach

This study develops and estimates a fixed-effects panel data regression model to analyze virtual gift purchase data for a large social network service.

Findings

Gift-giver centrality, gift-giving dispersion and gift-seeding increase virtual gift purchases. Increases in consumers’ receipt of seed gifts from social network firms (“direct seeding”) and from other consumers (“indirect seeding”) increases virtual gift purchases. However, the extent to which consumers give seed gifts to their friends in the social network (“seed mediation”) does not affect sales. Greater gift-giver centrality amplifies (attenuates) the positive effects of direct (indirect) seeding. At greater levels of gift-giving dispersion, the effects of indirect seeding and seed mediation become negative. Furthermore, gift-seeding has spillover effects on virtual good (non-gift) purchases.

Research limitations/implications

This study’s data, drawn from a South Korean social network service, offer unique and valuable social network information on actual virtual gift purchases and their seeding. Future research should replicate the results of the study outside the South Korean context.

Practical implications

Given the effects reported in this study, social network firms can facilitate the purchases of virtual gifts by improving the targeting of consumers in social networks and gift-seeding tactics.

Originality/value

This study uniquely examines the individual and interactive effects of network-related variables and gift-seeding on virtual gift sales. The study is seminal in its examination of how gift-seeding can be used as a marketing tactic to increase virtual gift purchases.
A semi-implicit characteristic-based polynomial pressure projection for FEM to solve incompressible flows
Authors: Liu Mingyang , Zhu Huifen , Gao Guangjun , Jiang Chen , Liu G.R
Published: February 2021

Purpose

The purpose of this paper is to investigate a novel stabilization scheme to handle convection and pressure oscillation in the process of solving incompressible laminar flows by finite element method (FEM).

Design/methodology/approach

The semi-implicit stabilization scheme, characteristic-based polynomial pressure projection (CBP3) consists of the Characteristic-Galerkin method and polynomial pressure projection. Theoretically, the proposed scheme works for any type of element using equal-order approximation for velocity and pressure. In this work, linear 3-node triangular and 4-node tetrahedral elements are the focus, which are the simplest but most difficult elements for pressure stabilizations.

Findings

The present paper proposes a new scheme, which can stabilize FEM solution for flows of both low and relatively high Reynolds numbers. And the influence of stabilization parameters of the CBP3 scheme has also been investigated.

Research limitations/implications

The research in this work is limited to the laminar incompressible flow.

Practical implications

The verification and validation of the CBP3 scheme are conducted by several 2 D and 3 D numerical examples. The scheme could be used to deal with more practical fluid problems.

Social implications

The application of scheme to study complex hemodynamics of patient-specific abdominal aortic aneurysm is also presented, which demonstrates its potential to solve bio-flows.

Originality/value

The paper simulated 2 D and 3 D numerical examples with superior results compared to existing results and experiments. The novel CBP3 scheme is verified to be very effective in handling convection and pressure oscillation.