Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-Dimensional Structure of N-Terminal Domain of DnaB Helicase and Helicase-Primase Interactions in Helicobacter pylori

Replication initiation is a crucial step in genome duplication and homohexameric DnaB helicase plays a central role in the replication initiation process by unwinding the duplex DNA and interacting with several other proteins during the process of replication. N-terminal domain of DnaB is critical for helicase activity and for DnaG primase interactions. We present here the crystal structure of the N-terminal domain (NTD) of H. pylori DnaB (HpDnaB) helicase at 2.2 Å resolution and compare the structural differences among helicases and correlate with the functional differences. The structural details of NTD suggest that the linker region between NTD and C-terminal helicase domain plays a vital role in accurate assembly of NTD dimers. The sequence analysis of the linker regions from several helicases reveals that they should form four helix bundles. We also report the characterization of H. pylori DnaG primase and study the helicase-primase interactions, where HpDnaG primase stimulates DNA unwinding activity of HpDnaB suggesting presence of helicase-primase cohort at the replication fork. The protein-protein interaction study of C-terminal domain of primase and different deletion constructs of helicase suggests that linker is essential for proper conformation of NTD to interact strongly with HpDnaG. The surface charge distribution on the primase binding surface of NTDs of various helicases suggests that DnaB-DnaG interaction and stability of the complex is most probably charge dependent. Structure of the linker and helicase-primase interactions indicate that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative bacteria.
Differential Dynamics of Transposable Elements during Long-Term Diploidization of Nicotiana Section Repandae (Solanaceae) Allopolyploid Genomes

Evidence accumulated over the last decade has shown that allopolyploid genomes may undergo drastic reorganization. However, timing and mechanisms of structural diploidization over evolutionary timescales are still poorly known. As transposable elements (TEs) represent major and labile components of plant genomes, they likely play a pivotal role in fuelling genome changes leading to long-term diploidization. Here, we exploit the 4.5 MY old allopolyploid Nicotiana section Repandae to investigate the impact of TEs on the evolutionary dynamics of genomes. Sequence-specific amplified polymorphisms (SSAP) on seven TEs with expected contrasted dynamics were used to survey genome-wide TE insertion polymorphisms. Comparisons of TE insertions in the four allopolyploid species and descendents of the diploid species most closely related to their actual progenitors revealed that the polyploids showed considerable departure from predicted additivity of the diploids. Large numbers of new SSAP bands were observed in polyploids for two TEs, but restructuring for most TE families involved substantial loss of fragments relative to the genome of the diploid representing the paternal progenitor, which could be due to changes in allopolyploids, diploid progenitor lineages or both. The majority of non-additive bands were shared by all polyploid species, suggesting that significant restructuring occurred early after the allopolyploid event that gave rise to their common ancestor. Furthermore, several gains and losses of SSAP fragments were restricted to N. repanda, suggesting a unique evolutionary trajectory. This pattern of diploidization in TE genome fractions supports the hypothesis that TEs are central to long-term genome turnover and depends on both TE and the polyploid lineage considered.
Jack of All Trades, Master of All: A Positive Association between Habitat Niche Breadth and Foraging Performance in Pit-Building Antlion Larvae

Species utilizing a wide range of resources are intuitively expected to be less efficient in exploiting each resource type compared to species which have developed an optimal phenotype for utilizing only one or a few resources. We report here the results of an empirical study whose aim was to test for a negative association between habitat niche breadth and foraging performance. As a model system to address this question, we used two highly abundant species of pit-building antlions varying in their habitat niche breadth: the habitat generalist Myrmeleon hyalinus, which inhabits a variety of soil types but occurs mainly in sandy soils, and the habitat specialist Cueta lineosa, which is restricted to light soils such as loess. Both species were able to discriminate between the two soils, with each showing a distinct and higher preference to the soil type providing higher prey capture success and characterizing its primary habitat-of-origin. As expected, only small differences in the foraging performances of the habitat generalist were evident between the two soils, while the performance of the habitat specialist was markedly reduced in the alternative sandy soil. Remarkably, in both soil types, the habitat generalist constructed pits and responded to prey faster than the habitat specialist, at least under the temperature range of this study. Furthermore, prey capture success of the habitat generalist was higher than that of the habitat specialist irrespective of the soil type or prey ant species encountered, implying a positive association between habitat niche-breadth and foraging performance. Alternatively, C. lineosa specialization to light soils does not necessarily confer upon its superiority in utilizing such habitats. We thus suggest that habitat specialization in C. lineosa is either an evolutionary dead-end, or, more likely, that this species' superiority in light soils can only be evident when considering additional niche axes.
Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

Background Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Methodology/Principal Findings In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. Conclusions/Significance As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.
Identification of Character Adjectives from Mahabharata

The present paper describes the identification of prominent characters and their adjectives from Indian mythological epic, Mahabharata, written in English texts. However, in contrast to the tra-ditional approaches of named entity identifica-tion, the present system extracts hidden attributes associated with each of the characters (e.g., character adjectives). We observed distinct phrase level linguistic patterns that hint the pres-ence of characters in different text spans. Such six patterns were used in order to extract the cha-racters. On the other hand, a distinguishing set of novel features (e.g., multi-word expression, nodes and paths of parse tree, immediate ancestors etc.) was employed. Further, the correlation of the features is also measured in order to identify the important features. Finally, we applied various machine learning algorithms (e.g., Naive Bayes, KNN, Logistic Regression, Decision Tree, Random Forest etc.) along with deep learning to classify the patterns as characters or non-characters in order to achieve decent accuracy. Evaluation shows that phrase level linguistic patterns as well as the adopted features are highly active in capturing characters and their adjectives.
Exploring laterality and memory effects in the haptic discrimination of verbal and non-verbal shapes

ABSTRACT The brain’s left hemisphere often displays advantages in processing verbal information, while the right hemisphere favours processing non-verbal information. In the haptic domain due to contra-lateral innervations, this functional lateralization is reflected in a hand advantage during certain functions. Findings regarding the hand-hemisphere advantage for haptic information remain contradictory, however. This study addressed these laterality effects and their interaction with memory retention times in the haptic modality. Participants performed haptic discrimination of letters, geometric shapes and nonsense shapes at memory retention times of 5, 15 and 30 s with the left and right hand separately, and we measured the discriminability index d′. The d′ values were significantly higher for letters and geometric shapes than for nonsense shapes. This might result from dual coding (naming + spatial) or/and from a low stimulus complexity. There was no stimulus-specific laterality effect. However, we found a time-dependent laterality effect, which revealed that the performance of the left hand-right hemisphere was sustained up to 15 s, while the performance of the right-hand-left hemisphere decreased progressively throughout all retention times. This suggests that haptic memory traces are more robust to decay when they are processed by the left hand-right hemisphere.
Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase–deficient mice on 129Sv/C57BL/6 background

Exaggerated maternal immune responses must be strictly controlled to ensure a successful pregnancy. Neutrophil extracellular traps (NETs) have recently been implicated as a potential mechanism for promoting inflammation in pregnancy‐related disorders. In this study, we demonstrated that NETs play a key role in the pathogenesis of sphingosine kinase (Sphk)‐mediated pregnancy loss. Perturbing the sphingolipid pathway by disrupting Sphk genes during pregnancy led to excessive NET formation exclusively at the fetomaternal interface and early fetal death. Neutrophils that formed NETs were characterized by histone hypercitrullination and peptidylarginine deiminase 4 (PAD4) overexpression. In addition, thrombus formation was enhanced in the decidua, but not in the plasma, of Sphk‐deficient mice. Blocking NET formation with a PAD4 inhibitor protected Sphk‐deficient mice from pregnancy loss. The PAD4 inhibition significantly reduced the expression of hypercitrullinated histone in neutrophils and ameliorated vascular injury in the decidua of Sphk‐deficient mice. Moreover, NET formation was induced in human neutrophils stimulated with Sphk‐deficient human decidual cells. Together, these findings indicate that targeting NETs might be a novel therapeutic strategy to treat idiopathic pregnancy loss in humans. —Mizugishi, K. , Yamashita, K. Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase–deficient mice on 129Sv/C57BL/6 background. FASEB J. 31, 5577–5591 (2017). www.fasebj. org
CYLINDRICAL BENDING OF THICK ORTHOTROPIC PLATE USING TRIGONOMETRIC SHEAR DEFORMATION THEORY

Flexure of cylindrical bending of thick orthotropic plates using trigonometric shear deformation theory taking into account transverse shear deformation effect as well as transverse normal strain effect is presented in this paper. The displacement field contains three unknowns. The axial displacement field uses sinusoidal function in terms of thickness coordinate to include the shear deformation effect. The cosine function in thickness coordinates is used in transverse displacement to include the effect of transverse normal strain. Governing equations and boundary conditions of the theory are obtained using the principle of virtual work. Results obtained for static flexure of simply supported orthotropic plates in cylindrical bending are compared with those of other refined theories and elasticity solution.
Establishment of Comprehensive Indicators in TCM Pectoral-qi Case Report Based on Experts Diagnosis and Self-test Technology

Rationale: To establish TCM Pectoral-qi comprehensive indicators and highlight the inner structure among different variables in an objective way, the article uses Partial Least Square Second-order Latent Variable Model (PLS-SLVM) and accomplishes 3 different comprehensive indicators based on both experts diagnosis and self-test data. SLVM includes a measurement model that defines the relationship between observed variables and latent variables and a structure model that imputes relationships between latent variables. The article focuses on PLS as the estimation method. Without normal distribution and independence assumptions, PLS uses objective weighting methods based on the data. Bootstrap method (B = 200) is used to calculate the mean value and standard errors of the PLS estimates. The article chooses the percentile interval to obtain the confidence interval of PLS parameters. Patient concerns: The patients were diagnosed by the means of experts diagnosis and self-test technology. On the one hand, the patients want to know the effect of self-test by wearing a kind of instrument. On the other hand, we want to establish TCM Pectoral-qi comprehensive indicators and highlight the inner structure among different variables in an objective way. Diagnoses: The group of 59 subjects are the same no matter whether they were diagnosed through TCM Pectoral-qi Assessment Questionnaire of self-test technology. Interventions: The same group of 59 subjects keep wearing the instrument for hours and get the self-test data consequently. Outcomes: As one of comprehensive indicator establishing methods, PLS-SLVM highlights the structure state among variables and improves the evaluation efficiency. Furthermore, it provides a new tool and method in TCM diseases prevention and health security. Lessons: As expected, PLS-SLVM is a useful tool due to its nonassumption of normal distribution and independence with consideration of correlation among different variables. Thus PLS-SLVM can be applied in ordinal data from assessment questionnaire and continuous data about physicochemical indexes for the same group of people. It displays that PLS-SLVM builds a connection between TCM experts diagnosis and the self-testing technology.
Predicting drug safety and communicating risk: benefits of a Bayesian approach

Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualisations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.
Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?

Restrictive allograft syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation, with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis.
Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction.
Losing the battle: Perceived status loss and contemplated or attempted suicide in older adults

While loss of socioeconomic status (SES) has been linked to suicidal behavior, it is unclear whether this experience is merely a downstream effect of psychopathology (“downward drift”), a sign of hardship, or an independent psychological contributor to suicide risk. We examined the association between the subjective experience of status loss and suicidal behavior and ideation in old age, while accounting for potential confounders. We were also interested in whether status loss was associated with mere thoughts of suicide vs. suicidal behavior.
Novel thick-foam ferroelectret with engineered voids for energy harvesting applications

This work reports a novel thick-foam ferroelectret which is designed and engineered for energy harvesting applications. We fabricated this ferroelectret foam by mixing a chemical blowing agent with a polymer solution, then used heat treatment to activate the agent and create voids in the polymer foam. The dimensions of the foam, the density and size of voids can be well controlled in the fabrication process. Therefore, this ferroelectret can be engineered into optimized structure for energy harvesting applications.
Rapid 3D in vivo Magnetic Particle Imaging with a Large Field of View

Introduction Magnetic particle imaging (MPI) is a new tomographic imaging approach that quantitatively maps concentrations of iron oxide nanoparticle distributions [1]. It combines high sensitivity [2,3] with the ability of fast volumetric imaging. In vivo 3D real-time MPI of a bolus of particles flowing through the heart and lung of mice has been demonstrated [4], but with an imaging approach that is limited to small fields of view (FoVs). A new scanner type with a bore diameter of 12 cm allowing rapid imaging with larger FoVs has been developed [5]. This contribution presents initial in vivo rat measurements on the new system.
Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice

ABSTRACT Upon release of HIV-1 particles from the infected cell, the viral protease cleaves the Gag polyprotein at specific sites, triggering maturation. During this process, which is essential for infectivity, the capsid protein (CA) reassembles into a conical core. Maturation inhibitors (MIs) block HIV-1 maturation by interfering with protease-mediated CA-spacer peptide 1 (CA-SP1) processing, concomitantly stabilizing the immature CA-SP1 lattice; virions from MI-treated cells retain an immature-like CA-SP1 lattice, whereas mutational abolition of cleavage at the CA-SP1 site results in virions in which the CA-SP1 lattice converts to a mature-like form. We previously reported that propagation of HIV-1 in the presence of MI PF-46396 selected for assembly-defective, compound-dependent mutants with amino acid substitutions in the major homology region (MHR) of CA. Propagation of these mutants in the absence of PF-46396 resulted in the acquisition of second-site compensatory mutations. These included a Thr-to-Ile substitution at SP1 residue 8 (T8I), which results in impaired CA-SP1 processing. Thus, the T8I mutation phenocopies PF-46396 treatment in terms of its ability to rescue the replication defect imposed by the MHR mutations and to impede CA-SP1 processing. Here, we use cryo-electron tomography to show that, like MIs, the T8I mutation stabilizes the immature-like CA-SP1 lattice. These results have important implications for the mechanism of action of HIV-1 MIs; they also suggest that T8I may provide a valuable tool for structural definition of the CA-SP1 boundary region, which has thus far been refractory to high-resolution analysis, apparently because of conformational flexibility in this region of Gag. IMPORTANCE HIV-1 maturation involves dissection of the Gag polyprotein by the viral protease and assembly of a conical capsid enclosing the viral ribonucleoprotein. Maturation inhibitors (MIs) prevent the final cleavage step at the site between the capsid protein (CA) and spacer peptide 1 (SP1), apparently by binding at this site and denying the protease access. Additionally, MIs stabilize the immature-like CA-SP1 lattice, preventing release of CA into the soluble pool. We previously found that T8I, a mutation in SP1, rescues a PF-46396-dependent CA mutant and blocks CA-SP1 cleavage. In this study, we imaged T8I virions by cryo-electron tomography and showed that T8I mutants, like MI-treated virions, contain an immature CA-SP1 lattice. These results lay the groundwork needed to understand the structure of the CA-SP1 interface region and further illuminate the mechanism of action of MIs.