bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients' Experiences Before, During, and After a Colonoscopy Procedure
Authors: Rosvall Annica , Axelsson Malin , Toth Ervin , Kumlien Christine , Annersten Gershater Magdalena
Published: December 2021

Although colonoscopy is a common examination, there is limited research focusing on how patients experience this procedure. It is important that a colonoscopy is tolerated, as it may lead to lifesaving diagnostics and treatment. This study aims to explore adult patients' experience of undergoing a colonoscopy regarding the time prior to, during, and after the procedure. This was a qualitative study with individual interviews (n = 24) and a purposeful sample that was analyzed using thematic analysis. The analysis revealed four themes. The first, “making up one's mind,” describes how the participants gathered information and reflected emotionally about the forthcoming procedure. The hope of clarification motivated them to proceed. In the theme “getting ready,” self-care was in focus while the participants struggled to follow the instructions and carry out the burdensome cleansing. The next theme, “going through,” illuminates' experiences during the colonoscopy and highlights the importance of feeling involved and respected. The last theme, “finally over,” is characterized by experiences of relief, tiredness, and a desire for clarity. The healthcare professionals' ability to meet the participants' needs is vital, given that the experiences are highly individual. These findings contribute to a variegated image of how patients experience the process of undergoing a colonoscopy.
Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy
Authors: Gaier Eric D. , Rasool Nailyn , Rizzo Joseph F.
Published: December 2021

Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with “occult” GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.
Using whole-genome sequencing to assess the diversity of Paenibacillus larvae within an outbreak and a beekeeping operation
Authors: Papić Bojan , Golob Majda , Zdovc Irena , Avberšek Jana , Pislak Ocepek Metka , Kušar Darja
Published: December 2021

The spore-forming bacterium

Paenibacillus larvae

is the causative agent of American foulbrood (AFB), a devastating disease of honeybees (Apis mellifera). In the present study, we used whole-genome sequencing (WGS) to investigate an extensive outbreak of AFB in northwestern Slovenia in 2019. A total of 59

P

.

larvae

isolates underwent WGS, of which 40 originated from a single beekeeping operation, to assess the diversity of

P. larvae

within the beekeeping operation, apiary and colony. By applying a case-specific single-linkage threshold of 34 allele differences (AD), whole-genome multilocus sequence typing (wgMLST) identified two outbreak clusters represented by ERIC II-ST11 clones. All isolates from a single beekeeping operation fell within cluster 1 and the median pairwise AD between them was 10 (range=1–22). The median pairwise AD for apiaries of the same beekeeping operation ranged from 8 to 11 (min.=1, max.=22). For colonies of the same apiary and honey samples from these colonies, the median pairwise AD ranged from 8 to 14 (min.=1, max.=20). The maximum within-cluster distance was 33 pairwise AD for cluster 1 and 44 for cluster 2 isolates. The minimum distance between the outbreak-related and non-related isolates was 37 AD, confirming the importance of associated epidemiological data for delineating outbreak clusters. The observed transmission events could be explained by the activities of honeybees and beekeepers. The present study provides insight into the genetic diversity of

P. larvae

at different levels and thus provides information for future AFB surveillance.
Single-cell genomics-based analysis reveals a vital ecological role of Thiocapsa sp. LSW in the meromictic Lake Shunet, Siberia
Authors: Wu Yu-Ting , Chiang Pei-Wen , Tandon Kshitij , Rogozin Denis Yu , Degermendzhy Andrey G. , Tang Sen-Lin
Published: December 2021

Meromictic lakes usually harbour certain prevailing anoxygenic phototrophic bacteria in their anoxic zone, such as the purple sulfur bacterium (PSB)

Thiocapsa

sp. LSW (hereafter LSW) in Lake Shunet, Siberia. PSBs have been suggested to play a vital role in carbon, nitrogen and sulfur cycling at the oxic–anoxic interface of stratified lakes; however, the ecological significance of PSBs in the lake remains poorly understood. In this study, we explored the potential ecological role of LSW using a deep-sequencing analysis of single-cell genomics associated with flow cytometry. An approximately 2.7 Mb draft genome was obtained based on the co-assembly of five single-cell genomes. LSW might grow photolithoautotrophically and could play putative roles not only as a carbon fixer and diazotroph, but also as a sulfate reducer/oxidizer in the lake. This study provides insights into the potential ecological role of

Thiocapsa

sp. in meromictic lakes.
Added diagnostic accuracy after [18F]flutemetamol PET scanning in young patients with dementia in an academic memory clinic setting
Authors: Handels Ron L.H. , Zwan Marissa D. , Pelkmans Wiesje , Biessels Geert Jan , van Domburg Peter , Hoff Erik , Roks Gerwin , Schoonenboom Niki , Verweij Niek , van Berckel Bart N.M. , van der Flier Wiesje M. , Verhey Frans , Scheltens Philip , Bouwman Femke H.
Published: December 2021

Introduction

A timely diagnosis of Alzheimer’s Disease (AD) in an early stage of dementia is important to support timely access to treatment, advice, and care. The aim of this study was to estimate the diagnostic accuracy of [18F]flutemetamol PET in addition to the usual diagnostic workup for the diagnosis of AD in a memory clinic population with young onset dementia by means of a panel reference-based etiology diagnosis.

Methods

in an academic memory clinic early onset dementia cohort (n=211) the nosological diagnosis was set by usual diagnostic workup and after including [18F]flutemetamol amyloid PET in a stepwise approach. To assess the change in proportion correctly diagnosed, the diagnosis with and without [18F]flutemetamol PET was related to a panel-based reference standard, serving as gold standard, consisting of 3 neurologists who relied on available clinical information over 2-year follow-up (n=152; blinded for PET).

Results

The panel majority nosology was set as a reference diagnosis in 122 participants, leaving 30 (20%) participants with no majority reached. In 107 (88%) cases post-PET was in line with the reference, and in 103 (84%) the pre-PET diagnosis was in line with the reference. The difference was 3.3% (95% CI -3.5% to 10.1%; p=0.424).

Discussion

[18F]flutemetamol PET did not significantly improve the diagnostic accuracy in young patients with dementia in an academic memory clinic setting. The secondary analyses provided several indications for future research in a narrower subsample of persons with (very) high diagnostic uncertainty and to assess patient relevant health outcomes.
One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage
Authors: Vione Beatrice , Ramacieri Giuseppe , Zavaroni Giacomo , Piano Angela , La Rocca Giorgia , Caracausi Maria , Vitale Lorenza , Piovesan Allison , Gori Caterina , Pirazzoli Gian Luca , Strippoli Pierluigi , Cocchi Guido , Corvaglia Luigi , Locatelli Chiara , Pelleri Maria Chiara , Antonaros Francesca
Published: December 2021

Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all one-carbon cycle. We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n=108, control n=41), 5-methyltetrahydrofolate (5-methyl-THF; DS n=140, control n=34), 5-formyltetrahydrofolate (5-formyl-THF; DS n=80, control n=21), S-adenosyl-homocysteine (SAH; DS n=94, control n=20) and S-adenosyl-methionine (SAM; DS n=24, control n=15). Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS.
Regional Topological Aberrances of White Matter- and Gray Matter-based Functional Networks for Attention Processing may Foster Traumatic Brain Injury-Related Attention Deficits in Adults
Authors: Wu Ziyan , Cao Meng , Di Xin , Wu Kai , Gao Yu , Li Xiaobo
Published: December 2021

Traumatic brain injury (TBI) is highly prevalent in adults. TBI-related functional brain alterations have been linked with common post-TBI neurobehavioral sequelae, with unknown neural sub-strates. This study examined the systems-level functional brain alterations in white matter (WM) and gray matter (GM) for visual sustained attention processing, their interactions, and contribution to post-TBI attention deficits. Task-based functional MRI data were collected from 42 adults with TBI and 43 group-matched normal controls (NCs), and analyzed using the graph theoretic tech-nique. Global and nodal topological properties were calculated and compared between the two groups. Correlation analyses were conducted between the neuroimaging measures that showed significant between-group differences and the behavioral symptom measures in attention domain in the groups of TBI and NCs, respectively. Significantly altered nodal efficiency and/or degree in several WM and GM nodes were reported in the TBI group, including the posterior corona radiata (PCR), posterior thalamic radiation (PTR), postcentral gyrus (PoG), and superior temporal sulcus (STS). Subjects with TBI also demonstrated abnormal systems-level functional synchronization between the PTR and STS in the right hemisphere, hypo-interaction between PCR and PoG in the left hemisphere; as well as the involvement of systems-level functional aberrances in PCR in TBI-related behavioral impairments in the attention domain. Findings of the current study suggest that TBI-related systems-level functional alterations associated with these two major association WM tracts and their anatomically connected GM regions may play critical role in TBI-related behavioral deficits in attention domain.
Rethinking Margin of Stability: Incorporating Step-To-Step Regulation to Resolve the Paradox
Authors: Kazanski Meghan , Cusumano Joseph P. , Dingwell Jonathan B.
Published: December 2021

Derived from inverted pendulum dynamics, mediolateral Margin of Stability (MoSML) is a mechanically-grounded measure of instantaneous stability. However, average MoSML measures yield paradoxical results. Gait pathologies or perturbations often induce larger (supposedly “more stable”) average MoSML, despite clearly destabilizing factors. However, people do not walk “on average” – they walk (and sometimes lose balance) one step at a time. We assert the paradox arises because averaging discards step-to-step dynamics. We present a framework unifying the inverted pendulum with Goal-Equivalent Manifold (GEM) analyses. We identify in the pendulum’s center-of-mass dynamics constant-MoSML manifolds, including one candidate “stability GEM” signifying the goal to maintain some constant . We used this framework to assess step-to-step MoSML dynamics of humans walking in destabilizing environments. While goal-relevant deviations were readily corrected, humans did not exploit equifinality by allowing deviations to persist along this GEM. Thus, maintaining a constant is inconsistent with observed step-to-step fluctuations in center-of-mass states. Conversely, the extent to which participants regulated fluctuations in foot placements strongly predicted regulation of center-of-mass fluctuations. Thus, center-of-mass dynamics may arise indirectly as a consequence of regulating mediolateral foot placements. To resolve the paradox caused by averaging MoSML, we present a new statistic, Probability of Instability (PoIL), to predict instability likelihood. Participants exhibited increased PoIL when destabilized (p = 9.45×10−34), despite exhibiting larger (“more stable”) average MoSML (p = 1.70×10−15). Thus, PoIL correctly captured people’s increased risk of losing lateral balance, whereas average MoSML did not. PoIL also explains why peoples’ average MoSML increased in destabilizing contexts.
Benchmarking Geometric Deep Learning for Cortical Segmentation and Neurodevelopmental Phenotype Prediction
Authors: Fawaz Abdulah , Williams Logan Z. J. , Alansary Amir , Bass Cher , Gopinath Karthik , da Silva Mariana , Dahan Simon , Adamson Chris , Alexander Bonnie , Thompson Deanne , Ball Gareth , Desrosiers Christian , Lombaert Hervé , Rueckert Daniel , Edwards A. David , Robinson Emma C.
Published: December 2021

The emerging field of geometric deep learning extends the application of convolutional neural networks to irregular domains such as graphs, meshes and surfaces. Several recent studies have explored the potential for using these techniques to analyse and segment the cortical surface. However, there has been no comprehensive comparison of these approaches to one another, nor to existing Euclidean methods, to date. This paper benchmarks a collection of geometric and traditional deep learning models on phenotype prediction and segmentation of sphericalised neonatal cortical surface data, from the publicly available Developing Human Connectome Project (dHCP). Tasks include prediction of postmenstrual age at scan, gestational age at birth and segmentation of the cortical surface into anatomical regions defined by the M-CRIB-S atlas. Performance was assessed not only in terms of model precision, but also in terms of network dependence on image registration, and model interpretation via occlusion. Networks were trained both on sphericalised and anatomical cortical meshes. Findings suggest that the utility of geometric deep learning over traditional deep learning is highly task-specific, which has implications for the design of future deep learning models on the cortical surface. The code, and instructions for data access, are available from https://github.com/Abdulah-Fawaz/Benchmarking-Surface-DL.
Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence
Authors: Kesner Andrew J. , Mateo Yolanda , Abrahao Karina P. , Ramos-Maciel Stephanie , Pava Matthew J. , Gracias Alexa L. , Paulsen Riley T. , Carlson Hartley B. , Lovinger David M.
Published: December 2021

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.
Delta variant with P681R critical mutation revealed by ultra-large atomic-scale ab initio simulation: Implications for the fundamentals of biomolecular interactions
Authors: Adhikari Puja , Jawad Bahaa , Rao Praveen , Podgornik Rudolf , Ching Wai-Yim
Published: December 2021

SARS-CoV-2 Delta variant is emerging as a globally dominant strain. Its rapid spread and high infection rate are attributed to a mutation in the spike protein of SARS-CoV-2 allowing the virus to invade human cells much faster and with increased efficiency. Particularly, an especially dangerous mutation P681R close to the furin cleavage site has been identified as responsible for increasing the infection rate. Together with the earlier reported mutation D614G in the same domain, it offers an excellent instance to investigate the nature of mutations and how they affect the interatomic interactions in the spike protein. Here, using ultra large-scale ab initio computational modeling, we study the P681R and D614G mutations in the SD2-FP domain including the effect of double mutation and compare the results with the wild type. We have recently developed a method of calculating the amino acid-amino acid bond pairs (AABP) to quantitatively characterize the details of the interatomic interactions, enabling us to explain the nature of mutation at the atomic resolution. Our most significant find is that the mutations reduce the AABP value, implying a reduced bonding cohesion between interacting residues and increasing the flexibility of these amino acids to cause the damage. The possibility of using this unique mutation quantifiers in a machine learning protocol could lead to the prediction of emerging mutations.
Estimating muscle activation from EMG using deep learning-based dynamical systems models
Authors: Wimalasena Lahiru N. , Braun Jonas F. , Keshtkaran Mohammad Reza , Hofmann David , Gallego Juan Álvaro , Alessandro Cristiano , Tresch Matthew C. , Miller Lee E. , Pandarinath Chethan
Published: December 2021

Objective

To study the neural control of movement, it is often necessary to estimate how muscles are activated across a variety of behavioral conditions. However, estimating the latent command signal that underlies muscle activation is challenging due to its complex relation with recorded electromyographic (EMG) signals. Common approaches estimate muscle activation independently for each channel or require manual tuning of model hyperparameters to optimally preserve behaviorally-relevant features.

Approach

Here, we adapted AutoLFADS, a large-scale, unsupervised deep learning approach originally designed to de-noise cortical spiking data, to estimate muscle activation from multi-muscle EMG signals. AutoLFADS uses recurrent neural networks (RNNs) to model the spatial and temporal regularities that underlie multi-muscle activation.

Main Results

We first tested AutoLFADS on muscle activity from the rat hindlimb during locomotion, and found that it dynamically adjusts its frequency response characteristics across different phases of behavior. The model produced single-trial estimates of muscle activation that improved prediction of joint kinematics as compared to low-pass or Bayesian filtering. We also tested the generality of the approach by applying AutoLFADS to monkey forearm muscle activity from an isometric task. AutoLFADS uncovered previously uncharacterized high-frequency oscillations in the EMG that enhanced the correlation with measured force compared to low-pass or Bayesian filtering. The AutoLFADS-inferred estimates of muscle activation were also more closely correlated with simultaneously-recorded motor cortical activity than other tested approaches.

Significance

Ultimately, this method leverages both dynamical systems modeling and artificial neural networks to provide estimates of muscle activation for multiple muscles that can be used for further studies of multi-muscle coordination and its control by upstream brain areas.
A nickase Cas9 gene-drive system promotes super-Mendelian inheritance in Drosophila
Authors: Del Amo Víctor López , Juste Sara Sanz , Gantz Valentino M.
Published: December 2021

CRISPR-based gene-drive systems have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance towards super-Mendelian rates (>50%). Current technologies employ a Cas9 that introduces DNA double-strand breaks into the opposing wildtype allele to replace it with a copy of the gene drive allele via DNA homology-directed repair. Yet, the use of different Cas9s versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a novel gene-drive approach that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5’ overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous for targeting essential genes. Indeed, our nickase approach should expand the repertoire for gene-drive designs aimed at applications in mosquitoes and beyond.
Detection of allele-specific expression in spatial transcriptomics with spASE
Authors: Zou Luli S. , Zhao Tongtong , Cable Dylan M. , Murray Evan , Aryee Martin J. , Chen Fei , Irizarry Rafael A.
Published: December 2021

Allele-specific expression (ASE), or the preferential expression of one allele, can be observed in transcriptomics data from early development throughout the lifespan. However, the prevalence of spatial and cell type-specific ASE variation remains unclear. Spatial transcriptomics technologies permit the study of spatial ASE patterns genome-wide at near-single-cell resolution. However, the data are highly sparse, and confounding between cell type and spatial location present further statistical challenges. Here, we introduce spASE (https://github.com/lulizou/spase), a computational framework for detecting spatial patterns in ASE within and across cell types from spatial transcriptomics data. To tackle the challenge presented by the low signal to noise ratio due to the sparsity of the data, we implement a spatial smoothing approach that greatly improves statistical power. We generated Slide-seqV2 data from the mouse hippocampus and detected ASE in X-chromosome genes, both within and across cell type, validating our ability to recover known ASE patterns. We demonstrate that our method can also identify cell type-specific effects, which we find can explain the majority of the spatial signal for autosomal genes. The findings facilitated by our method provide new insight into the uncharacterized landscape of spatial and cell type-specific ASE in the mouse hippocampus.
Age-elevated prostaglandin E2enhances mortality to influenza infection
Authors: Chen Judy , Deng Jane C. , Zemans Rachel , Zhang Min , Peters-Golden Marc , Goldstein Daniel R.
Published: December 2021

Aging impairs the immune responses to influenza A virus (IAV), resulting in increased mortality to IAV infections in older adults. With aging, there is reduced number and impaired function of alveolar macrophages (AMs), cells critical for defense against IAV. However, factors within the aged lung that impair AMs are not fully known. Using a murine model of IAV infection, we observed that aging increased the level of prostaglandin E2(PGE2) in the bronchoalveolar lavage fluid (BALF) of aged mice compared to young mice. Blockade of the PGE2receptor EP2 in aged mice increased AM numbers and subsequently enhanced survival to IAV. Additionally, PGE2impaired the mitochondrial health of AMs. We also identified senescent type II alveolar epithelial cells (AECs) as a source of the aged-associated PGE2in the lung. Our results reveal a crosstalk between AECs and AMs, via PGE2, that compromises host defense to IAV infection with aging.
Dataset-adaptive minimizer order reduces memory usage in k-mer counting
Authors: Flomin Dan , Pellow David , Shamir Ron
Published: December 2021

The rapid, continuous growth of deep sequencing experiments requires development and improvement of many bioinformatics applications for analysis of large sequencing datasets, including k-mer counting and assembly. Several applications reduce RAM usage by binning sequences. Binning is done by employing minimizer schemes, which rely on a specific order of the minimizers. It has been demonstrated that the choice of the order has a major impact on the performance of the applications. Here we introduce a method for tailoring the order to the dataset. Our method repeatedly samples the dataset and modifies the order so as to flatten the k-mer load distribution across minimizers. We integrated our method into Gerbil, a state-of-the-art memory efficient k-mer counter, and were able to reduce its memory footprint by 30% - 50% for large k, with only minor increase in runtime. Our tests also showed that the orders produced by our method produced superior results when transferred across datasets from the same species, with little or no order change. This enables memory reduction with essentially no increase in runtime.
Genetic architecture of dispersal and local adaptation drives accelerating range expansions
Authors: Deshpande Jhelam N. , Fronhofer Emanuel A.
Published: December 2021

Contemporary evolution has the potential to significantly alter biotic responses to global change, including range expansion dynamics and biological invasions. However, predictive models often make highly simplifying assumptions about the genetic architecture underlying relevant traits. This can be problematic since genetic architecture defines evolvability, that is, evolutionary rates, and higher order evolutionary processes, which determine whether evolution will be able to keep up with environmental change or not. Therefore, we here study the impact of the genetic architecture of dispersal and local adaptation, two central traits of high relevance for range expansion dynamics, on the speed and variability of range expansions into an environmental gradient, such as temperature. In our theoretical model we assume that dispersal and local adaptation traits result from the products of two non-interacting gene-regulatory networks (GRNs). We compare our model to simpler quantitative genetics models and show that in the GRN model, range expansions are accelerated, faster and more variable. Increased variability implies that these evolutionary changes reduce predictability. We further find that acceleration in the GRN model is primarily driven by an increase in the rate of local adaptation to novel habitats which results from greater sensitivity to mutation (decreased robustness) and increased gene expression. Our results highlight how processes at microscopic scales, here, within genomes, can impact the predictions of large scale, macroscopic phenomena, such as range expansions, by modulating the rate of evolution.
UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions
Authors: Mestre Mario Rodríguez , Gao Linyi , Shah Shiraz A. , López-Beltrán Adrián , González-Delgado Alejandro , Martínez-Abarca Francisco , Iranzo Jaime , Redrejo-Rodríguez Modesto , Zhang Feng , Toro Nicolás
Published: December 2021

Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.
Quinacrine binds to the kinase domain of FGFR1 and inhibits its activity
Authors: Kumar Makhan , Sarkar Angshuman
Published: December 2021

Background

FGF family receptors, especially FGFR1, have been widely implicated for their potential role in the promotion of oncogenesis and chemoresistance in lung cancer. Quinacrine, an anti-malarial drug, has been widely reported to exhibit anti-neoplastic properties through the activation of p53 and simultaneous inhibition of NF-kB signaling pathways in cancer cells.

Methods

The binding of QC to FGFR1 was studied using molecular docking and molecular dynamics simulation studies. The experimental kinase activity assay for the protein was performed using a luminescence-based kinase assay. FGF-induced phosphorylation and proliferation were studied by cell counting and western blotting. Matrigel-based cell migration was conducted to assess migration activity.

Results

QC interacted with multiple residues around the kinase insert domain of FGFR1 through hydrogen bonding, hydrophobic interactions, and water bridges. The kinase activity inhibition assay demonstrated a significant reduction in FGFR1 kinase activity by QC at higher concentrations, which was further observed at the cellular level in inhibition of FGFR1 phosphorylation and proliferation by QC at higher exposure concentrations of FGF stimulated cells. These effects were further validated downstream in the FGF-induced activation of cell migration.

Conclusion

QC did form a stable interaction with residues of FGFR1 at another allosteric site surrounding the kinase domain, leading to inhibition of its kinase activity at higher drug concentrations. This effect was further observed at the cellular level in both acidic and basic FGF ligand-induced proliferation, phosphorylation of FGFR1, and cell migration, where a trend of significant reduction in activity was observed at higher drug concentrations.
Reduction of free-roaming cat population requires high-intensity neutering in spatial contiguity to mitigate compensatory effects
Authors: Gunther Idit , Hawlena Hadas , Azriel Lior , Gibor Dan , Berke Olaf , Klement Eyal
Published: December 2021

When free-roaming in natural areas, the domestic cat (Felis silvestris catus) is ranked high among the most destructive alien species. Near human dwellings, it might risk humans, impair sanitation, and suffer from poor welfare. Cats’ popularity as companion animals complicates their population control. Thus, culling is often replaced by a fertility control method called “Trap-Neuter-Return/Release (TNR),” which is considered more humane. Despite the extensive application of TNR, a long-term controlled study was never performed to test its effectiveness. We present a uniquely designed controlled field experiment for examining TNR effectiveness. The study was performed over a twelve-year period, divided into pre-intervention, mixed- and full-intervention phases, and spanned a 20Km2urban area. Trends of cat, intact-female, and kitten counts, cat reproduction, and carcass reports were compared among study phases and areas with different neutering intensities. The cat population increased during the first two study phases and did not decline in highly neutered populations, presumably due to cat immigration. Expansion of high-intensity neutering to the entire city in the full-intervention phase (>70% neutering percentage) reversed cat population growth, reaching an annual ca. 7% reduction. This population reduction was limited by a rebound increase in cat reproduction and longevity. We conclude that cat population management by TNR should be performed in high-intensity, continuously, and in geographic contiguity to enable population reduction. To enhance management effectiveness and mitigate compensatory effects, we recommend further evaluating an integrated strategy that combines TNR with complementary methods (e.g., vital resource regulation, ill cat euthanasia, and adoption).

Significance Statement

Though popular companion animals, domestic cats pose numerous problems when free-roaming, including predation of wildlife, hazards to humans, impaired sanitation, and a decrease in their welfare. Thus, managing their populations is essential. The Trap-Neuter-Return method (TNR, capturing, sterilizing, returning/releasing) is widely employed for managing cat populations. However, there is a lack of long-term controlled evidence for its effectiveness. We examined the outcomes of high-intensity TNR by performing a twelve-year controlled field experiment, the largest to date. Neutering over 70% of the cats caused population decline when applied over contiguous areas. However, it was limited by a rebound increase in reproduction and survival. These findings provide a robust quantification of the limitations and the long-term effectiveness of TNR.
A Non-Canonical Function of Arabidopsis ERECTA Proteins in Gibberellin Signaling
Authors: Sarnowska Elzbieta , Kubala Szymon , Cwiek Pawel , Sacharowski Sebastian , Oksinska Paulina , Steciuk Jaroslaw , Zaborowska Magdalena , Szurmak Jakub M. , Dubianski Roman , Maassen Anna , Stachowiak Malgorzata , Huettel Bruno , Ciesla Monika , Kogut Klaudia , Rolicka Anna T. , Alseekh Saleh , Bucior Ernest , Franzen Rainer , Klepacz Anna , Domagalska Malgorzata A. , Amar Samija , Siedlecki Janusz A. , Fernie Alisdair R. , Davis Seth J. , Sarnowski Tomasz J.
Published: December 2021

The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs), comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1) and ERECTA-LIKE 2 (ERL2), control epidermal patterning, inflorescence architecture, stomata development, and hormonal signaling. Here we show that the er/erl1/erl2 triple mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. ERf proteins interact in the nucleus, via kinase domains, with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 triple mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. Correlation between DELLA overaccumulation and SWI3B proteasomal degradation together with the physical interaction of SWI3B with DELLA proteins explain the lack of RGA accumulation in the GA- and SWI3B-deficient erf mutant plants. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in transcriptional control of gene expression, and observed similar features for human HER2 (Epidermal Growth Family Receptor-member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.

ONE SENTENCE SUMMARY

ERECTA leucine-rich receptor-like kinase and SWI3B subunit of SWI/SNF chromatin remodeling complex cooperate in direct transcriptional control of GID1 genes in Arabidopsis.
In vitro neurons learn and exhibit sentience when embodied in a simulated game-world
Authors: Kagan Brett J. , Kitchen Andy C. , Tran Nhi T. , Parker Bradyn J. , Bhat Anjali , Rollo Ben , Razi Adeel , Friston Karl J.
Published: December 2021

Integrating neurons into digital systems to leverage their innate intelligence may enable performance infeasible with silicon alone, along with providing insight into the cellular origin of intelligence. We developed DishBrain, a system which exhibits natural intelligence by harnessing the inherent adaptive computation of neurons in a structured environment. In vitro neural networks from human or rodent origins, are integrated with in silico computing via high-density multielectrode array. Through electrophysiological stimulation and recording, cultures were embedded in a simulated game-world, mimicking the arcade game ‘Pong’. Applying a previously untestable theory of active inference via the Free Energy Principle, we found that learning was apparent within five minutes of real-time gameplay, not observed in control conditions. Further experiments demonstrate the importance of closed-loop structured feedback in eliciting learning over time. Cultures display the ability to self-organise in a goal-directed manner in response to sparse sensory information about the consequences of their actions.
Simultaneous Super-Resolution and Distortion Correction for Single-shot EPI DWI using Deep Learning
Authors: Ye Xinyu , Wang Peipei , Li Sisi , Zhang Jieying , Lian Yuan , Zhang Yajing , Lu Jie , Guo Hua
Published: December 2021

Single-shot echo planer imaging (SS-EPI) is widely used for clinical Diffusion-weighted magnetic resonance imaging (DWI) acquisitions. However, due to the limited bandwidth along the phase encoding direction, the obtained images suffer from distortion and blurring, which limits its clinical value for diagnosis. Here we proposed a deep learning-based image-quality-transfer method with a novel loss function with improved network structure to simultaneously increase the resolution and correct distortions for SS-EPI. We proposed a modified network structure based on Generative Adversarial Networks (GAN). A dense net with gradient map guidance and a multi-level fusion block was employed as the generator to suppress the over-smoothing effect. We also proposed a fractional anisotropy (FA) loss to exploit the intrinsic signal relations in DWI. In-vivo brain DWI data were used to test the proposed method. The results showed that the distortion-corrected high-resolution DWI images with restored anatomical details can be obtained from low-resolution SS-EPI images by taking the advantage of high-resolution anatomical images. Additionally, the proposed FA loss can improve the image quality and quantitative accuracy of diffusion metrics by utilizing the intrinsic relations among different diffusion directions.
ABC Transporters are billion-year-old Maxwell Demons
Authors: Flatt Solange , Busiello Daniel M. , Zamuner Stefano , De Los Rios Paolo
Published: December 2021

ABC transporters are a broad family of biological machines, found in most prokaryotic and eukaryotic cells, performing the crucial import or export of substrates through both plasma and organellar membranes, and maintaining a steady concentration gradient driven by ATP hydrolysis. Building upon the present biophysical and biochemical characterization of ABC transporters, we propose here a model whose solution reveals that these machines are an exact molecular realization of the Maxwell Demon, a century-old abstract device that uses an energy source to drive systems away from thermodynamic equilibrium. In particular, the Maxwell Demon does not perform any direct mechanical work on the system, but simply selects which spontaneous processes to allow and which ones to forbid based on information that it collects and processes. In the molecular model introduced here, the different information-processing steps that characterize Maxwell Demons (measurement, feedback and resetting) are features that emerge from the biochemical and structural properties of ABC transporters, allowing us to develop an explicit bridge between the molecular level description and the higher-level language of information theory.
Nontraditional lenders and access to local agricultural credit markets by beginning and female farmers
Authors: Nadolnyak Denis , Hartarska Valentina
Published: December 2021

Purpose

The purpose of this study is to evaluate if access to local branch infrastructure of the farm credit system institutions (FCS), banks and credit unions (BCU), and alternative financial services (AFS) providers is related to the use of credit from non-traditional lenders (NTLs). The focus is on beginning and women operators who are typically credit constrained and thus more likely to suffer from closures of bank branches and consolidation of traditional agricultural lenders.

Design/methodology/approach

Informed by Detragiache et al. (2000), the authors specify farmers’ use of loans as a function of their access to credit (measured by the branch density of each lender type) along with operator’s and operation’s controls. The measures of loans by NTLs (number, use, share and lender type) require the use of Poisson, Probit, Tobit and Multinomial Logit techniques. This study utilizes individual producer data from the 2018 Agricultural Resource Management Survey and 2018 county-level branch density data for FCS, BCU and AFS providers.

Findings

Access to credit from FCS is helpful to BFRs only, while access to AFS is associated with the use of loans from NTLs by women but not by BFRs. As expected, access to BCU credit matters for the use of loans from NTLs, with a complementary effect for BFRs but a substitution effect for women’s use of such loans.

Originality/value

There are no studies on local agricultural credit markets in the US that evaluate the implications from changes in access to credit on credit-constrained borrowers and their use of NTLs’ credit.
BioGames: a new paradigm and a behavioral biometrics collection tool for research purposes
Authors: Stylios Ioannis , Kokolakis Spyros , Skalkos Andreas , Chatzis Sotirios
Published: December 2021

Purpose

The purpose of this paper is to present a new paradigm, named BioGames, for the extraction of behavioral biometrics (BB) conveniently and entertainingly. To apply the BioGames paradigm, the authors developed a BB collection tool for mobile devices named BioGames App. The BioGames App collects keystroke dynamics, touch gestures, and motion modalities and is available on GitHub. Interested researchers and practitioners may use it to create their datasets for research purposes.

Design/methodology/approach

One major challenge for BB and continuous authentication (CA) research is the lack of actual BB datasets for research purposes. The compilation and refinement of an appropriate set of BB data constitute a challenge and an open problem. The issue is aggravated by the fact that most users are reluctant to participate in long demanding procedures entailed in the collection of research biometric data. As a result, they do not complete the data collection procedure, or they do not complete it correctly. Therefore, the authors propose a new paradigm and introduce a BB collection tool, which they call BioGames, for the extraction of biometric features in a convenient way. The BioGames paradigm proposes a methodology where users play games without participating in an experimental painstaking process. The BioGames App collects keystroke dynamics, touch gestures, and motion modalities.

Findings

The authors proposed a new paradigm for the collection of BB on mobile devices and created the BioGames application. The BioGames App is an Android application that collects BB data on mobile devices and sends them to a database. The database design allows multiple users to store their sensor data at any time. Thus, there is no concern about data separation and synchronization. BioGames App is General Data Protection Regulation (GDPR) compliant as it collects and processes only anonymous data.

Originality/value

The BioGames App is a publicly available tool that combines the keystroke dynamics, touch gestures, and motion modalities. In addition, it uses a methodology where users play games without participating in an experimental painstaking process.
Group diversity and employee service innovative behavior in the hospitality industry: a multilevel model
Authors: Yang Mingjun , Luu Tuan Trong , Qian David
Published: December 2021

Purpose

Service innovative behavior from employees helps hospitality organizations gain a competitive advantage and sustain business flourishment. Although group diversity has been demonstrated as a predictor of employee outcomes, whether group diversity in terms of extraversion and openness enhances employee service innovative behavior remains a gap. This study aims to fill this gap by developing a multilevel model of the direct relationship between group diversity in terms of extraversion and openness and employee service innovative behavior and also the mediations and moderations behind the relationship.

Design/methodology/approach

The authors collectd data from 44 Chinese hospitality teams. The research model was validated by multilevel structural equation modeling.

Findings

Results showed that both group extraversion diversity and group openness diversity fostered employee service innovative behavior via creative self-efficacy. Developmental culture strengthened the effectiveness of group openness diversity on creative self-efficacy and the effectiveness of creative self-efficacy on employee service innovative behavior. Nevertheless, developmental culture did not strengthen the effectiveness of group extraversion diversity on creative self-efficacy.

Practical implications

Findings suggest that managers and team leaders from hospitality organizations can elicit employee service innovative behavior through increasing group diversity in terms of extraversion and openness. Hospitality practitioners also should understand that employees’ confidence for creativity is able to channel group diversity into employee service innovative endeavors. Moreover, building developmental culture is essential for hospitality teams to strengthen the effect of group diversity on innovating services.

Originality/value

This study expands the diversity-innovation research through unfolding both the mediations and the moderations behind the link between group diversity in terms of extraversion and openness and employee service innovative behavior.