Miracle-dz/UniFAR-FTUs huggingface dataset:
A Bacterial Dynamin-Like Protein Confers a Novel Phage Resistance Strategy on the Population Level in Bacillus subtilis

Bacteria have to cope with myriads of phages in their natural environments. Consequently, they have evolved sophisticated systems to prevent phage infection or epidemic spreading of the infection in the population. ABSTRACT Bacillus subtilis DynA is a member of the dynamin superfamily, involved in membrane remodeling processes. DynA was shown to catalyze full membrane fusion and it plays a role in membrane surveillance against antibiotics. We show here that DynA also provides a novel resistance mechanism against phage infection. Cells lacking DynA are efficiently lysed after phage infection and virus replication. DynA does not prevent phage infection and replication in individual cells, but significantly delays host cell lysis, thereby slowing down the release of phage progeny from the host cells. During the process, DynA forms large, almost immobile clusters on the cell membrane that seem to support membrane integrity. Single-molecule tracking revealed a shift of freely diffusive molecules within the cytosol toward extended, confined motion at the cell membrane following phage induction. Thus, the bacterial dynamins are the first anti-phage system reported to delay host cell lysis and the last line of defense of a multilayered antiviral defense. DynA is therefore providing protective effects on the population, but not on single cell level. IMPORTANCE Bacteria have to cope with myriads of phages in their natural environments. Consequently, they have evolved sophisticated systems to prevent phage infection or epidemic spreading of the infection in the population. We show here that a bacterial dynamin-like protein is involved in phage resistance. The Bacillus subtilis DynA protein delays lysis of infected bacteria and reduces spreading of the phage particles. Thus, the dynamin mediated protection is not at the level of the individual cell, but on the population level. The bacterial DynA is the last line of defense to reduce the deleterious effect of a phage infection in a bacterial community. Interestingly, dynamin-like proteins such as Mx proteins are also involved in antiviral activities in Eukaryotes. Thus, the interaction of dynamin-like proteins and viruses seem to be an evolutionary ancient process.
The structural role of bacterial eDNA in the formation of biofilm streamers

Across diverse habitats, bacteria are mainly found as biofilms, surface-attached communities embedded in a self-secreted matrix of extracellular polymeric substances (EPS), which enhances bacterial resistance to antimicrobial treatment and mechanical stresses. In the presence of flow and geometric constraints such as corners or constrictions, biofilms take the form of long, suspended threads known as streamers, which bear important consequences in industrial and clinical settings by causing clogging and fouling. The formation of streamers is thought to be driven by the viscoelastic nature of the biofilm matrix. Yet, little is known about the structural composition of streamers and how it affects their mechanical properties. Here, using a microfluidic platform that allows growing and precisely examining biofilm streamers, we show that extracellular DNA (eDNA) constitutes the backbone and is essential for the mechanical stability of Pseudomonas aeruginosa’ s streamers. This finding is supported by the observations that DNA-degrading enzymes prevent the formation of streamers and clear already formed ones, and that the antibiotic ciprofloxacin promotes their formation by increasing the release of eDNA. Furthermore, using mutants for production of the exopolysaccharide Pel, an important component of P. aeruginosa’ s EPS, we reveal a new, although indirect role of Pel, in tuning the mechanical properties of the streamers. Taken together, these results highlight the importance of eDNA and of its interplay with Pel in determining the mechanical properties of P. aeruginosa streamers, and suggest that targeting the composition of streamers can be an effective approach to control the formation of these biofilm structures.
SegmA: Residue Segmentation of cryo-EM density maps

The cryo-EM resolution revolution enables the development of algorithms for direct de-novo modelling of protein structures from given cryo-EM density maps. Deep Learning tools have been applied to locate structure patterns, such as rotamers, secondary structures and Cα atoms. We present a deep neural network (nicknamed SegmA) for the residue type segmentation of a cryo-EM density map. The network labels voxels in a cryo-EM map by the residue type (amino acid type or nucleic acid) of the sampled macromolecular structure. It also provides a visual representation of the density map by coloring the different types of voxels by their assigned colors. SegmA’s algorithm is a cascade of CNNs and group rotational equivariant CNNs. A data gathering algorithm was designed for creating datasets that will give best results when used for SegmA’s training. At resolution of 3.2°A SegmAs accuracy is 80% for nucleotides. Amino acids which can be seen by eye, such as LEU, ARG and PHE, are detected by SegmA with about 70% accuracy. In addition SegmA detects regions where the exact labeling is of low confidence due to resolution, noise, etc. Removing those “unconfident” regions increases the amino acid detection accuracy to 80% The SegmA open code is available at https://github.com/Mark-Rozanov/SegmA_3A/tree/master.
Quantitative profiling of adaptation to cyclin E overproduction

Detailed analysis of individual human cells responding then adapting to the stress of chronic cyclin E overproduction, which inhibits DNA replication origin licensing by inducing premature S phase. Cyclin E/CDK2 drives cell cycle progression from G1 to S phase. Despite the toxicity of cyclin E overproduction in mammalian cells, the cyclin E gene is overexpressed in some cancers. To further understand how cells can tolerate high cyclin E, we characterized non-transformed epithelial cells subjected to chronic cyclin E overproduction. Cells overproducing cyclin E, but not cyclins D or A, briefly experienced truncated G1 phases followed by a transient period of DNA replication origin underlicensing, replication stress, and impaired proliferation. Individual cells displayed substantial intercellular heterogeneity in cell cycle dynamics and CDK activity. Each phenotype improved rapidly despite high cyclin E–associated activity. Transcriptome analysis revealed adapted cells down-regulated a cohort of G1-regulated genes. Withdrawing cyclin E from adapted cells only partially reversed underlicensing indicating that adaptation is at least partly non-genetic. This study provides evidence that mammalian cyclin E/CDK inhibits origin licensing indirectly through premature S phase onset and provides mechanistic insight into the relationship between CDKs and licensing. It serves as an example of oncogene adaptation that may recapitulate molecular changes during tumorigenesis.
Age- and sex-related topological organisation of human brain functional networks and their relationship to cognition

BACKGROUND Age and sex associated with changes in functional brain network topology and cognition in large population of older adults have been poorly understood. We explored this question further by examining differences in 11 resting-state graph theory measures with respect to age, sex, and their relationships with cognitive performance in 17,127 UK Biobank participants (mean=62.83±7.41 years). METHODS Brain connectivity toolbox was used to derive the graph theory measures that assessed network integration, segregation, and strength. Multiple linear regression was performed the relationship between age, sex, cognition, and network measures. Subsequently, multivariate analysis was done to further examine the joint effect of the network measures on cognitive functions. RESULTS Age was associated with an overall decrease in the effectiveness of network communication (i.e. integration) and loss of functional specialisation (i.e. segregation) of specific brain regions. Sex differences were also observed, with women showing more efficient networks which were less segregated than in men (FDR adjusted p<.05). Age-related changes were also more apparent in men than women, which suggests that men may be more vulnerable to cognitive decline with age. Interestingly, while network segregation and strength of limbic network were only nominally associated with cognitive performance, the network measures collectively were significantly associated with cognition (FDR adjusted p≤.002). This may imply that individual measures may be inadequate to capture much of the variance in neural activity or its output and need further refinement. CONCLUSION The complexity of the functional brain organisation may be shaped by an individual’s age and sex, which ultimately may influence cognitive performance of older adults. Age and sex stratification may be used to inform clinical neuroscience research to identify older adults at risk of cognitive dysfunction.
Kraken

It is well-known that without strict network bandwidth guarantees, application performance in multi-tenant cloud environments is unpredictable. While recently proposed systems support explicit bandwidth reservation mechanisms, they require the resource schedules to be announced ahead of time. We argue that this is not practical in today's cloud environments, where application demands are inherently unpredictable, e.g., due to stragglers. We in this paper present KRAKEN, a system that allows tenants to dynamically request and update minimum resource guarantees for both network bandwidth and compute resources at runtime. Unlike previous work, Kraken does not require prior knowledge about the resource needs of the tenants' applications but allows tenants to modify their reservation at runtime. Kraken achieves this through an online resource reservation scheme, and by optimally embedding and reconfiguring virtual networks.
Editorial: Working Dogs: Form and Function, Volume II

Working dogs span the spectrum of careers from high powered physical athletes working in protection fields to highly cognitive dogs working in the service sector. Regardless of the career, all working dogs share a common requirement for physical capabilities and mental aptitude and partnership with their handler. In this Research Topic, Working Dogs: Form and Function, twenty manuscripts address the development and assessment of the physical Form, behavioral selection of dogs that contribute to Function, a focus on olfactory Function, occupational hazards that interfere with Form and Function and the relationship between the working dog and handler that addresses Form and Function of the working dog team.
Enhanced Age-Related Resistance to Tomato Yellow Leaf Curl Virus in Tomato Is Associated With Higher Basal Resistance

Tomato yellow leaf curl virus (TYLCV) is one of the most notorious plant pathogens affecting the production of tomato worldwide. While the occurrence of age-related resistance (ARR) against TYLCV has been reported, the factors impacting its development remain unknown. We conducted a series of experiments with three tomato cultivars that vary in basal resistance to TYLCV to explore factors involved in the development of ARR. Our data indicate that ARR is more pronounced in tomato cultivars with higher basal resistance. Additionally, increased plant biomass in older plants does not contribute to ARR. Virus source plants with a younger age at initial inoculation facilitates virus acquisition by whiteflies. Finally, an analysis on plant hormones suggests that salicylic acid (SA) may play a major role in the development of ARR in tomato against TYLCV. These findings provide new insights into the developmental resistance in tomato against TYLCV as well as clues for the deployment of ARR in the management of diseases caused by TYLCV.
Editorial: Exploring the Potential of Particle Radiotherapy: Helium, Neutrons, Carbon, and Other Heavy Ions

Radiation therapy is a cornerstonemodality in the treatment of malignant diseases. Since the inception of thefieldover a centuryago, clinicians andresearchers have focusedon improving the therapeutic ratio of radiation therapy, therefore minimizing toxicities while maximizing tumor control. The use of particle therapy to improve the therapeutic ratio can be traced to 1946, when Dr. Robert Wilson first proposed the use of accelerated protons and heavy ions for oncological treatments in a landmark paper (1). Today, clinicians and researchers are investigating theuseof a varietyofdifferent ions for therapeutic use, including protons, carbon ions, fast neutrons, boron neutron capture, and multi-ion therapy (2). Each of the heavy ions have unique radiobiological and physical properties that must be taken into consideration, although theyall share somecommonfeatures, suchas ahigh linearenergy transfer (LET) and relative biological effectiveness (RBE). These properties theoretically make heavy ions more potent at causing DNA damage and hopefully improving tumor control (3, 4) Our topic accepted a total of 17 articles from 48 authors, demonstrating the emergence and importance of particle therapy in providing the best care for patients. Our topic can be divided into the following topics:
Effects of Biochar Feedstock and Pyrolysis Temperature on Soil Organic Matter Mineralization and Microbial Community Structures of Forest Soils

Biochar has received much attention as a strategy to enhance soil carbon (C) sequestration and mitigate climate change. Previous studies found that the feedstock and pyrolysis temperature can largely determine biochar properties, which in turn, impact the stability of native soil organic matter (SOM) and soil microorganisms. The Schima superba and Cunninghamia lanceolata are two tree species widely distributed in the subtropical region of southern China, but how the biochars from these two species influence the soil C sequestration and microbial communities of plantation remain poorly understood. In this study, we produced biochars from these two different feedstocks (13C-labeled S. superba and C. lanceolata litters) at three pyrolysis temperatures (350°C, 550°C, 750°C), then added them to the soils from C. lanceolata plantation, and maintained the experiments at 25°C for 112 days. We found both C mineralization and soil microbial community structures were strongly, but inconsistent, affected by biochar feedstock and pyrolysis temperature. The C. lanceolata biochar triggered the negative priming effect faster and greater compared with the S. superba biochar amendment. Biochars produced at 550°C showed the most significant negative priming effect during the whole incubation period, regardless of the different feedstocks. The cumulative amount of CO2 derived from biochars was significantly decreased with pyrolysis temperature (p < 0.05), indicating that biochars prepared at higher temperatures were more stable in the soil. Further, the soil microbial community structure was only affected by biochar pyrolysis temperature rather than biochar feedstock and their interaction. Together, our results reveal that biochar feedstock and pyrolysis temperature may play more important roles in dictating the priming effect than the structure of microbial community for C. lanceolata plantation. Overall, we concluded that the biochars prepared at 550°C could rapidly decrease the turnover of native SOM in a short term and biochar amendment has the potential to be a management practice for soil C sequestration in the C. lanceolata plantation.
Exploring the Interactions Between Neurophysiology and Cognitive and Behavioral Changes Induced by a Non-pharmacological Treatment: A Network Approach

Dementia due to Alzheimer’s disease (AD) is a neurological syndrome which has an increasing impact on society, provoking behavioral, cognitive, and functional impairments. AD lacks an effective pharmacological intervention; thereby, non-pharmacological treatments (NPTs) play an important role, as they have been proven to ameliorate AD symptoms. Nevertheless, results associated with NPTs are patient-dependent, and new tools are needed to predict their outcome and to improve their effectiveness. In the present study, 19 patients with AD underwent an NPT for 83.1 ± 38.9 days (mean ± standard deviation). The NPT was a personalized intervention with physical, cognitive, and memory stimulation. The magnetoencephalographic activity was recorded at the beginning and at the end of the NPT to evaluate the neurophysiological state of each patient. Additionally, the cognitive (assessed by means of the Mini-Mental State Examination, MMSE) and behavioral (assessed in terms of the Dementia Behavior Disturbance Scale, DBD-13) status were collected before and after the NPT. We analyzed the interactions between cognitive, behavioral, and neurophysiological data by generating diverse association networks, able to intuitively characterize the relationships between variables of a different nature. Our results suggest that the NPT remarkably changed the structure of the association network, reinforcing the interactions between the DBD-13 and the neurophysiological parameters. We also found that the changes in cognition and behavior are related to the changes in spectral-based neurophysiological parameters. Furthermore, our results support the idea that MEG-derived parameters can predict NPT outcome; specifically, a lesser degree of AD neurophysiological alterations (i.e., neural oscillatory slowing, decreased variety of spectral components, and increased neural signal regularity) predicts a better NPT prognosis. This study provides deeper insights into the relationships between neurophysiology and both, cognitive and behavioral status, proving the potential of network-based methodology as a tool to further understand the complex interactions elicited by NPTs.
Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study

Background Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR). Methods Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method. Results This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001). Conclusion Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.
Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components

Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.
Modelling the Fate of Pesticide Transformation Products From Plot to Catchment Scale—State of Knowledge and Future Challenges

Transformation products (TP) of pesticides are found everywhere in the aquatic environment. Their dynamic formation and subsequent transport from agricultural fields to adjacent water bodies can be estimated by using environmental fate models, which is done in the registration process for plant protection products in the European Union. In this study, peer-reviewed applications of such models, the model complexity and their structure are documented and analysed. In total, 20 publications of 10 models – eight leaching models (GLEAMS, MACRO, RZWQM2, PEARL, PRZM, Pelmo, LEACHM, HYDRUS 1-D) and two catchment scale models (Zin-AgriTra, FRM) – were identified. The reviewed models greatly differ in their process complexity regarding the formation rate and the formation pathways of TPs.The major reason given for models failing to reproduce sampled TP concentrations in case studies was an erroneous substance transport, especially missing preferential flow simulation in soil. However, the contribution of TP formation processes to simulation uncertainty was not analysed at all in most of the studies. By comparing the structure of existing models, the state of knowledge on TP fate and requirements of TP fate assessment, the following recommendations were drawn: i) It is suggested that the models should be updated to reflect the current state of knowledge in process research, especially more complex transformation schemes and the formation of different TPs in different compartments, which was not included in most of the models. ii) Even though there are pesticide parent compound fate models at the catchment scale with a temporal resolution of one day, none of these models is able to simulate TP fate. Such models would enable scientists and authorities to estimate the environmental fate of TPs at the larger catchment scale or the regional scale. iii) To get over the assessment of the huge number of TPs formed in the environment, an integration of Quantitative Structure Properties Relationship models predicting TP fate characteristics, TP pathway prediction models and environmental fate models is suggested. This would allow for a largely automated and comprehensive assessment of the fate of a pesticide parent compound and all its TPs for regulatory purposes.