bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-dependent endoplasmic reticulum Ca2+ uptake depends on Kv2.1-mediated endoplasmic reticulum/plasma membrane junctions to promote synaptic transmission
Authors: Panzera Lauren C. , Johnson Ben , Cho In Ha , Tamkun Michael M. , Hoppa Michael B. 
Published: October 2021

AbstractThe endoplasmic reticulum (ER) forms a continuous and dynamic network throughout a neuron, extending from dendrites to axon terminals, and axonal ER dysfunction is implicated in several neurological disorders. In addition, tight junctions between the ER and plasma membrane (PM) are formed by several molecules including Kv2 channels, but the cellular functions of many ER-PM junctions remain unknown. Dynamic Ca2+ uptake into the ER during electrical activity plays an essential role in synaptic transmission as failure to allow rapid ER Ca2+ filling during stimulation activates stromal interaction molecule 1 (STIM1) and decreases both presynaptic Ca2+ influx and synaptic vesicle exocytosis. Our experiments demonstrate that Kv2.1 channels are necessary for enabling ER Ca2+ uptake during electrical activity as genetic depletion of Kv2.1 rendered both the somatic and axonal ER unable to accumulate Ca2+ during electrical stimulation. Moreover, our experiments show that the loss of Kv2.1 in the axon impairs synaptic vesicle fusion during stimulation via a mechanism unrelated to modulation of membrane voltage. Thus, our data demonstrate that the non-conducting role of Kv2.1 in forming stable junctions between the ER and PM via ER VAMP-associated protein (VAP) binding couples ER Ca2+ uptake with electrical activity. Our results further suggest that Kv2.1 has a critical function in neuronal cell biology for Ca2+-handling independent of voltage and reveals a novel and critical pathway for maintaining ER lumen Ca2+ levels and efficient neurotransmitter release. Taken together these findings reveal an essential non-classical role for both Kv2.1 and the ER-PM junctions in synaptic transmission.SignificanceThe endoplasmic reticulum (ER) extends throughout the neuron as a continuous organelle, and its dysfunction is associated with several neurological disorders. During electrical activity, the ER takes up Ca2+ from the cytosol which has been shown to support synaptic transmission. This close choreography of ER Ca2+ uptake with electrical activity suggests functional coupling of the ER to sources of voltage-gated Ca2+ entry through an unknown mechanism. Here we report a non-conducting role for Kv2.1 through its ER binding domain that is necessary for ER Ca2+ uptake during neuronal activity. Loss of Kv2.1 profoundly disables neurotransmitter release without altering presynaptic voltage suggesting that Kv2.1-mediated signaling hubs play an important neurobiological role in Ca2+ handling and synaptic transmission independent of ion conduction.
DeePVP: Identification and classification of phage virion protein using deep learning
Authors: Fang Zhencheng , Feng Tao , Zhou Hongwei 
Published: October 2021

ABSTRACTThe poor annotation of phage virion protein (PVP) is the bottleneck of many areas of viral research, such as viral phylogenetic analysis, viral host identification and antibacterial drug design. Because of the high diversity of the PVP sequences, the PVP annotation remains a great challenging bioinformatic task. Based on deep learning, we present DeePVP that contains a main module and an extended module. The main module aims to identify the PVPs from non-PVP over a phage genome, while the extended module can further classify the predicted PVP into one of the ten major classes of PVP. Compared with the state-of-the-art tools that can distinguish PVP from non-PVP, DeePVP’s main module performs much better, with an F1-score 9.05% higher in the PVP identification task. Compared with PhANNs, a tool that can further classify the predicted PVP into a specific class, the overall accuracy of DeePVP’s extended module is approximately 3.72% higher in the PVP classification task. Two application cases on the genome of mycobacteriophage PDRPxv and Escherichia phage HP3 show that the predictions of DeePVP are much more reliable and can better reveal the compact PVP-enriched region, which may be conserved during the viral evolution process, over the phage genome.
An Hfq-dependent post-transcriptional mechanism fine tunes RecB expression inEscherichia coli
Authors: Kalita Irina , Iosub Ira Alexandra , McLaren Lorna , Goossens Louise , Granneman Sander , El Karoui Meriem 
Published: October 2021

AbstractAll living organisms have developed strategies to respond to chromosomal damage and preserve genome integrity. One such response is the repair of DNA double-strand breaks (DSBs), one of the most toxic forms of DNA lesions. InEscherichia coli, DSBs are repaired via RecBCD-dependent homologous recombination. RecBCD is essential for accurate chromosome maintenance, but its over-expression can lead to reduced DNA repair ability. This apparent paradox suggests that RecBCD copy numbers may need to be tightly controlled within an optimal range. Using single-molecule fluorescence microscopy, we have established that RecB is present in very low abundance at mRNA and protein levels. RecB transcription shows high fluctuations, yet cell-to-cell protein variability remains remarkably low. Here, we show that the post-transcriptional regulator Hfq binds torecBmRNA and down-regulates RecB protein translationin vivo. Furthermore, specific disruption of the Hfq-binding site leads to more efficient translation ofrecBmRNAs. In addition, we observe a less effective reduction of RecB protein fluctuations in the absence of Hfq. This fine-tuning Hfq-mediated mechanism might have the underlying physiological function of maintaining RecB protein levels within an optimal range.
Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination
Authors: Gürgen Dennis , Conrad Theresia , Becker Michael , Sebens Susanne , Röcken Christoph , Hoffmann Jens , Langhammer Stefan 
Published: October 2021

AbstractNon-small cell lung cancer (NSCLC) is commonly diagnosed at advanced stages limiting treatment options. Although, targeted therapy has become integral part of NSCLC treatment therapies often fail to improve patient’s prognosis. Based on previously published criteria for selecting drug combinations for overcoming resistances, NSCLC patient-derived xenograft (PDX) tumors were treated with a low dose combination of cabozantinib, afatinib, plerixafor and etoricoxib.All PDX tumors treated, including highly therapy-resistant adeno-and squamous cell carcinomas without identifiable driver mutations, were completely suppressed by this drug regimen, leading to an ORR of 81% and a CBR of 100%. The application and safety profile of this low dose therapy regimen was well manageable in the pre-clinical settings.Overall, this study provides evidence of a relationship between active paracrine signaling pathways of the cellular tumorigenic network, which can be effectively targeted by a low-dose multimodal therapy to overcome therapy resistance and improve prognosis of NSCLC.
Habitat determines convergent evolution of cephalic horns in vipers
Authors: Busschau Theo , Boissinot Stephane 
Published: October 2021

AbstractPhenotypic convergence of traits in similar environments can provide insights into the evolutionary processes shaping trait evolution. Among squamate reptiles, horn-like cephalic appendages have evolved under various selective pressures, including selection for defence, crypsis or sexual selection. Yet, among snakes, particularly vipers, the functional and evolutionary significance of horns are unknown. We used a comparative phylogenetic approach with habitat and diet data on 263 viper taxa to shed light on the selective pressures underlying horn evolution in vipers. We detected significant correlations with habitat but not diet. The relative positions of horns are ecologically divergent in that supranasal horns are positively correlated with terrestrial forest habitats while supraocular horns are negatively correlated with terrestrial forest habitats and associated with arboreal or sparsely vegetated habitats. Multiple independent origins of supranasal or supraocular horns in similar habitats provide evidence of adaptive convergence. Comparisons with other snake lineages suggest that cephalic appendages may have evolved under selection for crypsis in ambush foraging snakes.
ZELDA: a 3D Image Segmentation and Parent-Child relation plugin for microscopy image analysis in napari
Authors: D’Antuono Rocco , Pisignano Giuseppina 
Published: October 2021

AbstractBioimage analysis workflows allow the measurement of sample properties such as fluorescence intensity and polarization, cell number, and vesicles distribution, but often require the integration of multiple software tools. Furthermore, it is increasingly appreciated that to overcome the limitations of the 2D-view-based image analysis approaches and to correctly understand and interpret biological processes, a 3D segmentation of microscopy data sets becomes imperative.Despite the availability of numerous algorithms for the 2D and 3D segmentation, the latter still offers some challenges for the end-users, who often do not have either an extensive knowledge of the existing software or coding skills to link the output of multiple tools. While several commercial packages are available on the market, fewer are the open-source solutions able to execute a complete 3D analysis workflow.Here we present ZELDA, a new napari plugin that easily integrates the cutting-edge solutions offered by python ecosystem, such as scikit-image for image segmentation, matplotlib for data visualization, and napari multi-dimensional image viewer for 3D rendering. This plugin aims to provide interactive and zero-scripting customizable workflows for cell segmentation, vesicles counting, parent-child relation between objects, signal quantification, and results presentation; all included in the same open-source napari viewer, and “few clicks away”.
Operators’ risk awareness towards operations’ risk assessment: a field study in the motor vehicle field
Authors: Demichela Micaela , Comberti Lorenzo , Baldissone Gabriele 
Published: October 2021

PurposeThe purpose of the research was to verify if there was an alignment between the risk assessed and the risk perceived or if some inconsistencies arise that could affect the safety of the operators. In fact, eventual inconsistencies should be analysed, interpreted and managed to maximise the information and training process, if needed.Design/methodology/approachThe adopted approach in this work relies on the collection of the perception of the operators about the level of risk in a work environment and its comparison with the level of risk assessed by the company. The collection of data was performed through a survey designed ad hoc, subministrated to all the workers in the area under study, being them involved in the production and in the maintenance. The survey’s structure and aim were described to the operator by the researchers and returned by the operators in a voluntary and anonymous way.FindingsThe information collected allowed identifying a gap between the risk assessed and the risk perceived by the plant operators. For example, for the use of personal protective equipments, the data highlighted a discrepancy between the knowledge about their need and the behaviour in using them, which resulted in the revision of both communication and training processes, with the adoption of a more participatory approach.Originality/valueThe originality of the work is in the data set, originally collected for this study, in the data collection form, also devised specifically for the case under study, despite it can be easily adapted for other work environment, and in the purpose itself, aimed at pushing risk assessment towards a personalised and adaptive approach.
Contrasting patterns of risk from human and non‐human predators shape temporal activity of prey
Authors: Gaynor Kaitlyn M. , McInturff Alex , Brashares Justin S. 
Published: October 2021

AbstractSpatiotemporal variation in predation risk arises from interactions between landscape heterogeneity, predator densities and predator hunting mode, generating landscapes of fear for prey species that can have important effects on prey behaviour and ecosystem dynamics.As widespread apex predators, humans present a significant source of risk for hunted animal populations. Spatiotemporal patterns of risk from hunters can overlap or contrast with patterns of risk from other predators. Human infrastructure can also reshape spatial patterns of risk by facilitating or impeding hunter or predator movement, or deterring predators that are themselves wary of humans.We examined how anthropogenic and natural landscape features interact with hunting modes of rifle hunters and mountain lionsPuma concolorto generate spatiotemporal patterns of risk for their primary prey. We explored the implications of human‐modified landscapes of fear for Columbian black‐tailed deerOdocoileus hemionus columbianusin Mendocino County, California. We used historical harvest records, hunter GPS trackers and camera trap records of mountain lions to model patterns of risk for deer. We then used camera traps to examine deer spatial and temporal activity patterns in response to this variation in risk.Hunters and mountain lions exhibited distinct, contrasting patterns of spatiotemporal activity. Risk from rifle hunters, who rely on long lines of sight, was highest in open grasslands and near roads and was confined to the daytime. Risk from mountain lions, an ambush predator, was highest in dense shrubland habitat, farther from developed areas, and during the night and crepuscular periods. Areas of human settlement provided a refuge from both hunters and mountain lions. We found no evidence that deer avoided risk in space at the scale of our observations, but deer adjusted their temporal activity patterns to reduce the risk of encounters with humans and mountain lions in areas of higher risk.Our study demonstrates that interactions between human infrastructure, habitat cover and predator hunting mode can result in distinct spatial patterns of predation risk from hunters and other predators that may lead to trade‐offs for prey species. However, distinct diel activity patterns of predators may create vacant hunting domains that reduce costly trade‐offs for prey. Our study highlights the importance of temporal partitioning as a mechanism of predation risk avoidance.
Soil initial bacterial diversity and nutrient availability determine the rate of xenobiotic biodegradation
Authors: Jayaramaiah Ramesha H. , Egidi Eleonora , Macdonald Catriona A. , Wang Jun‐Tao , Jeffries Thomas C. , Megharaj Mallavarapu , Singh Brajesh K. 
Published: October 2021

SummaryUnderstanding the relative importance of soil microbial diversity, plants and nutrient management is crucial to implement an effective bioremediation approach to xenobiotics‐contaminated soils. To date, knowledge on the interactive effects of soil microbiome, plant and nutrient supply on influencing biodegradation potential of soils remains limited. In this study, we evaluated the individual and interactive effects of soil initial bacterial diversity, nutrient amendments (organic and inorganic) and plant presence on the biodegradation rate of pyrene, a polycyclic aromatic hydrocarbon. Initial bacterial diversity had a strong positive impact on soil biodegradation potential, with soil harbouring higher bacterial diversity showing ~ 2 times higher degradation rates than soils with lower bacterial diversity. Both organic and inorganic nutrient amendments consistently improved the degradation rate in lower diversity soils and had negative (inorganic) to neutral (organic) effect in higher diversity soils. Interestingly, plant presence/type did not show any significant effect on the degradation rate in most of the treatments. Structural equation modelling demonstrated that initial bacterial diversity had a prominent role in driving pyrene biodegradation rates. We provide novel evidence that suggests that soil initial microbial diversity, and nutrient amendments should be explicitly considered in the design and employment of bioremediation management strategies for restoring natural habitats disturbed by organic pollutants.
Extracellular vesicle production in Gram‐positive bacteria
Authors: Dean Scott N. , Thakur Meghna , Spangler Joseph R. 
Published: October 2021

SummaryThis is a highlight on the article ‘Extracellular vesicle formation in Lactococcus lactis is stimulated by prophage‐encoded holin‐lysin system’ by Yue Liu, Eddy Smid and Tjakko Abee.
Breeding phenology of a terrestrial‐breeding frog is associated with soil water potential: Implications for conservation in a changing climate
Authors: Hoffmann Emily P. , Mitchell Nicola J. 
Published: October 2021

AbstractAmphibian breeding is often linked to environmental cues. Given accelerating global climate change and habitat alteration, it is important to understand how environmental changes may affect male calling activity, the necessary precursor to mating. Here, we investigate the calling phenology and activity of Geocrinia alba, a critically endangered terrestrial‐breeding frog with a highly restricted distribution in southwestern Australia – a region undergoing significant warming and drying. We investigated whether calling periods differed across eight sites during a single breeding season, and the environmental conditions associated with calling activity at the start, peak and end of the calling period. We found consistent and prolonged calling activity over several months of the austral spring, but the length of the calling period varied two‐fold across sites, ranging from 3 to 6 months. Initiation of calling by G. alba was relatively similar across sites and was associated with warmer temperatures and higher soil water potential. However, the end of the calling period varied from October to January and was significantly associated with decreasing soil water potential. Calling only occurred when soils were close to saturation point, between −8 to −11 kPa, and therefore, breeding opportunities were likely also constrained by the length of time that soils were close to saturation. Changes in the regional climate, such as declining winter rainfall, could result in shorter breeding periods and consequently reduced breeding opportunities. More broadly, our study highlights the sensitivity of amphibians, particularly terrestrial‐breeding species, to changes in soil water potential and temperature, and the importance of maintaining suitable hydrological conditions during the breeding period.
Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies
Authors: Tamura Takashi , Wakai Kenji , Lin Yingsong , Tamakoshi Akiko , Utada Mai , Ozasa Kotaro , Sugawara Yumi , Tsuji Ichiro , Ono Ayami , Sawada Norie , Tsugane Shoichiro , Ito Hidemi , Nagata Chisato , Kitamura Tetsuhisa , Naito Mariko , Tanaka Keitaro , Shimazu Taichi , Mizoue Tetsuya , Matsuo Keitaro , Inoue Manami ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: October 2021

AbstractThe association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large‐scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study‐specific HRs using a random‐effects model. During 4 265 551 person‐years of follow‐up, 8586 stomach cancer cases were identified. In men, the multivariate‐adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87‐1.15) for occasional drinkers, and 1.00 (0.91‐1.11) for <23 g/d, 1.09 (1.01‐1.18) for 23 to <46 g/d, 1.18 (1.09‐1.29) for 46 to <69 g/d, 1.21 (1.05‐1.39) for 69 to <92 g/d, and 1.29 (1.11‐1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate‐adjusted HRs were 0.93 (0.80‐1.08) for occasional drinkers, and 0.85 (0.74‐0.99) for <23 g/d, and 1.22 (0.98‐1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15‐2.47) and 1.24 (0.99‐1.55) for ≥92 g/d in men, and 1.60 (0.76‐3.37) and 1.18 (0.88‐1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.
Prediction of the differences in tumor mutation burden between primary and metastatic lesions by radiogenomics
Authors: Hoshino Isamu , Yokota Hajime , Iwatate Yosuke , Mori Yasukuni , Kuwayama Naoki , Ishige Fumitaka , Itami Makiko , Uno Takashi , Nakamura Yuki , Tatsumi Yasutoshi , Shimozato Osamu , Nagase Hiroki 
Published: October 2021

AbstractTumor mutational burden (TMB) is gaining attention as a biomarker for responses to immune checkpoint inhibitors in cancer patients. In this study, we evaluated the status of TMB in primary and liver metastatic lesions in patients with colorectal cancer (CRC). In addition, the status of TMB in primary and liver metastatic lesions was inferred by radiogenomics on the basis of computed tomography (CT) images. The study population included 24 CRC patients with liver metastases. DNA was extracted from primary and liver metastatic lesions obtained from the patients and TMB values were evaluated by next‐generation sequencing. The TMB value was considered high when it equaled to or exceeded 10/100 Mb. Radiogenomic analysis of TMB was performed by machine learning using CT images and the construction of prediction models. In 7 out of 24 patients (29.2%), the TMB status differed between the primary and liver metastatic lesions. Radiogenomic analysis was performed to predict whether TMB status was high or low. The maximum values for the area under the receiver operating characteristic curve were 0.732 and 0.812 for primary CRC and CRC with liver metastasis, respectively. The sensitivity, specificity, and accuracy of the constructed models for TMB status discordance were 0.857, 0.600, and 0.682, respectively. Our results suggested that accurate inference of the TMB status is possible using radiogenomics. Therefore, radiogenomics could facilitate the diagnosis, treatment, and prognosis of patients with CRC in the clinical setting.