Miracle-dz/UniFAR-FTUs huggingface dataset:
Sialidases From Clostridium perfringens and Their Inhibitors

Clostridium perfringens is an important human and animal pathogen that is the primary causative agent of necrotizing enteritis and enterotoxemia in many types of animals; it causes traumatic gas gangrene in humans and animals and is associated with cases of food poisoning in humans. C. perfringens produces a variety of toxins as well as many enzymes, including three sialidases, NanH, NanI, and NanJ. Sialidases could be important virulence factors that promote the pathogenesis of C. perfringens. Among them, NanI promotes the colonization of C. perfringens in the intestinal tract and enhances the cytotoxic activity and association of several major C. perfringens toxins with host cells. In recent years, studies on the structure and functions of sialidases have yielded interesting results, and the functions of sialic acid and sialidases in bacterial pathogenesis have become a hot research topic. An in-depth understanding and additional studies of sialidases will further elucidate mechanisms of C. perfringens pathogenesis and could promote the development and clinical applications of sialidase inhibitors. This article reviews the structural characteristics, expression regulation, roles of sialidases in C. perfringens pathogenesis, and effects of their inhibitors.
The comparative susceptibility of Porphyromonas gingivalis to the killing mechanisms of the neutrophil

58 Introduction.59 Results.63 Discussion.72 Materials and Methods.83 Tables and Figures.91 References.100 3. The Relative Susceptibilities of Porphyromonas gingivalis to the Reactive Oxygen Species Associated With Neutrophil-Mediated Killing.114 Abstract.115 Introduction.116 Materials and Methods.124 Results.133 Discussion.139 Figures.148 References.159
The Common Basis of Memory and Consciousness: Understanding the Brain as a Write–Read Head Interacting With an Omnipresent Background Field

The main goal of this article consists in addressing two fundamental issues of consciousness research and cognitive science, namely, the question of why declarative memory functions are inextricably linked with phenomenal awareness and the question of the physical basis of memory traces. The presented approach proposes that high-level cognitive processes involving consciousness employ a universal mechanism by means of which they access and modulate an omnipresent background field that is identified with the zero-point field (ZPF) specified by stochastic electrodynamics (SED), a branch of physics that deals with the universal principles underlying quantum systems. In addition to its known physical properties and memory capacities, the ZPF is hypothesized to be an immanently sentient medium. It is propounded that linking up to a particular field mode of the ZPF activates a particular phenomenal nuance, implying that the phase-locked coupling of a set of field modes, i.e., the formation of a so-called ZPF information state, constitutes an appropriate mechanism for the amalgamation of elementary shades of consciousness into a complex state of consciousness. Since quantum systems rest exactly on this mechanism, conscious memory processes in the brain are expected to differ from unconscious processes by the presence of the typical features of many-body quantum systems, particularly long-range coherence and attractor formation, which is supported by a huge body of empirical evidence. On this basis, the conceptual framework set out in this article paves the way for a new understanding of the brain as a write–read head interacting with the ZPF, leading to self-consistent interpretations of the neural correlates of memory formation and memory retrieval and explaining why these memory processes are closely intertwined with phenomenal awareness. In particular, the neural correlates suggest that the brain produces consciously perceived memory traces by writing sequences of information states into the ZPF and retrieves consciously experienced memory traces by reading sequences of information states from the ZPF. Using these theoretical foundations, altered states of consciousness and memory disorders can be traced back to impairments of the ZPF write–read mechanism. The mechanism should reveal itself through characteristic photon emissions, resulting in testable predictions.
The prevalence of anti-thyroid peroxidase antibodies in subclinical and clinical hypothyroid patients -

Background: Subclinical hypothyroidism is a state of mild thyroid failure and is essentially a laboratory diagnosis with elevated serum thyroid stimulating hormone (TSH) and a normal free thyroxine (FT4) concentration. The main objective of study is to evaluate the prevalence of anti-thyroid peroxidise (anti-TPO) antibodies among patients with clinical and subclinical hypothyroidism. Methods: A prospective study was conducted involving 50 patients with biochemical evidence of hypothyroidism. Subclinical hypothyroidism was defined as thyroid stimulating hormone (TSH) >5.0 µIU/ml with normal FT4 and clinical hypothyroidism as free thyroxine (FT4) and high TSH. A detailed history, clinical examination, and investigations comprising of complete haemogram, fasting plasma glucose, fasting FT4, TSH, anti-TPO antibodies and lipid profile were done for all the patients. Results: Out of 50 cases, 28 subjects had clinical hypothyroidism (25 females and 3 males) and 22 had subclinical hypothyroidism (14 females and 8males). Among the 50 subjects with clinical and subclinical hypothyroidism, 33 were anti-TPO positive. The corresponding percentage of anti-TPO positivity noted in the clinical hypothyroidism and subclinical hypothyroidism groups were 80 % and 50% respectively. Conclusions: Serum TSH and anti-TPO analyses are essential in determining the etiology of hypothyroidism and risk of progression to overt hypothyroidism in patients with subclinical.
Reduced Global-Brain Functional Connectivity and Its Relationship With Symptomatic Severity in Cervical Dystonia

Background: Altered functional connectivity (FC) is related to pathophysiology of patients with cervical dystonia (CD). However, inconsistent results may be obtained due to different selected regions of interest. We explored voxel-wise brain-wide FC changes in patients with CD at rest in an unbiased manner and analyzed their correlations with symptomatic severity using the Tsui scale. Method: A total of 19 patients with CD and 21 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was applied to analyze the images. Support vector machine was used to distinguish the patients from the controls. Results: Patients with CD exhibited decreased GFC in the right precentral gyrus and right supplementary motor area (SMA) that belonged to the M1-SMA motor network. Significantly negative correlation was observed between GFC values in the right precentral gyrus and symptomatic severity in the patients (r = −0.476, p = 0.039, uncorrected). Decreased GFC values in these two brain regions could be utilized to differentiate the patients from the controls with good accuracies, sensitivities and specificities (83.33, 85.71, and 80.95% in the right precentral gyrus; and 87.59, 89.49, and 85.71% in the right SMA). Conclusions: Our investigation suggests that patients with CD show reduced GFC in brain regions of the M1-SMA motor network and provides further insights into the pathophysiology of CD. GFC values in the right precentral gyrus and right SMA may be used as potential biomarkers to recognize the patients from the controls.
Transformational Leadership, Career Adaptability, and Work Behaviors: The Moderating Role of Task Variety

Career adaptability is a set of individual resources that benefit one’s sustainable development in his/her lifelong careers, especially in today’s turbulent environment. However, how to foster employees’ career adaptability through managerial strategies and eventually contribute to organizations remains to be studied. Guided by the career construction theory, we posit a moderated mediation model that transformational leadership (TFL) could strengthen employees’ career adaptability and further foster their task performance and organization-directed citizenship behavior (OCBO), with task variety moderating the mediation effect. We conducted a three-wave survey with 558 supervisor-employee dyads to test the overall model. The results validated that career adaptability mediated the links between TFL and task performance as well as OCBO. Furthermore, the mediation effect was stronger for employees who had higher levels of task variety. In short, our study offers the groundwork to understand that employees’ career adaptability can be activated by transformational leaders and is self-regulatory to benefit work behaviors in the task variety context. It enlightens organizations to cultivate employees’ career adaptability in the way of TFL and job design, with the objective of promoting the sustainable development for both the employees and the organizations.
An Evolutionary View of Trypanosoma Cruzi Telomeres

Like in most eukaryotes, the linear chromosomes of Trypanosoma cruzi end in a nucleoprotein structure called the telomere, which is preceded by regions of variable length called subtelomeres. Together telomeres and subtelomeres are dynamic sites where DNA sequence rearrangements can occur without compromising essential interstitial genes or chromosomal synteny. Good examples of subtelomeres involvement are the expansion of human olfactory receptors genes, variant surface antigens in Trypanosoma brucei, and Saccharomyces cerevisiae mating types. T. cruzi telomeres are made of long stretches of the hexameric repeat 5′-TTAGGG-OH-3′, and its subtelomeres are enriched in genes and pseudogenes from the large gene families RHS, TS and DGF1, DEAD/H-RNA helicase and N-acetyltransferase, intermingled with sequences of retrotransposons elements. In particular, members of the Trans-sialidase type II family appear to have played a role in shaping the current T. cruzi telomere structure. Although the structure and function of T. cruzi telomeric and subtelomeric regions have been documented, recent experiments are providing new insights into T. cruzi's telomere-subtelomere dynamics. In this review, I discuss the co-evolution of telomere, subtelomeres and the TS gene family, and the role that these regions may have played in shaping T. cruzi's genome.
An Extra Cue Is Beneficial for Native Speakers but Can Be Disruptive for Second Language Learners: Integration of Prosody and Visual Context in Syntactic Ambiguity Resolution

It has long been debated whether non-native speakers can process sentences in the same way as native speakers do or they suffer from certain qualitative deficit in their ability of language comprehension. The current study examined the influence of prosodic and visual information in processing sentences with a temporarily ambiguous prepositional phrase (“Put the cake on the plate in the basket”) with native English speakers and Japanese learners of English. Specifically, we investigated (1) whether native speakers assign different pragmatic functions to the same prosodic cues used in different contexts and (2) whether L2 learners can reach the correct analysis by integrating prosodic cues with syntax with reference to the visually presented contextual information. The results from native speakers showed that contrastive accents helped to resolve the referential ambiguity when a contrastive pair was present in visual scenes. However, without a contrastive pair in the visual scene, native speakers were slower to reach the correct analysis with the contrastive accent, which supports the view that the pragmatic function of intonation categories are highly context dependent. The results from L2 learners showed that visually presented context alone helped L2 learners to reach the correct analysis. However, L2 learners were unable to assign contrastive meaning to the prosodic cues when there were two potential referents in the visual scene. The results suggest that L2 learners are not capable of integrating multiple sources of information in an interactive manner during real-time language comprehension.
Cholesterol-Dependent Cytolysins Produced by Vaginal Bacteria: Certainties and Controversies

Bacterial vaginosis (BV) is a vaginal anaerobic dysbiosis that affects women of reproductive age worldwide. BV is microbiologically characterized by the depletion of vaginal lactobacilli and the overgrowth of anaerobic bacterial species. Accumulated evidence suggests that Gardnerella spp. have a pivotal role among BV-associated bacteria in the initiation and development of BV. However, Gardnerella spp. often colonize healthy women. Lactobacillus iners is considered as a prevalent constituent of healthy vaginal microbiota, and is abundant in BV. Gardnerella spp. and L. iners secrete the toxins vaginolysin (VLY) and inerolysin (INY), which have structural and activity features attributed to cholesterol-dependent cytolysins (CDCs). CDCs are produced by many pathogenic bacteria as virulence factors that participate in various stages of disease progression by forming lytic and non-lytic pores in cell membranes or via pore-independent pathways. VLY is expressed in the majority of Gardnerella spp. isolates; less is known about the prevalence of the gene that encodes INY. INY is a classical CDC; membrane cholesterol acts a receptor for INY. VLY uses human CD59 as its receptor, although cholesterol remains indispensable for VLY pore-forming activity. INY-induced damage of artificial membranes is directly dependent on cholesterol concentration in the bilayer, whereas VLY-induced damage occurs with high levels of membrane cholesterol (>40 mol%). VLY primarily forms membrane-embedded complete rings in the synthetic bilayer, whereas INY forms arciform structures with smaller pore sizes. VLY activity is high at elevated pH, which is characteristic of BV, whereas INY activity is high at more acidic pH, which is specific for a healthy vagina. Increased VLY levels in vaginal mucosa in vivo were associated with clinical indicators of BV. However, experimental evidence is lacking for the specific roles of VLY and INY in BV. The interplay between vaginal bacterial species affects the expression of the gene encoding VLY, thereby modulating the virulence of Gardnerella spp. This review discusses the current evidence for VLY and INY cytolysins, including their structures and activities, factors affecting their expression, and their potential impacts on the progression of anaerobic dysbiosis.
Organ-On-A-Chip in vitro Models of the Brain and the Blood-Brain Barrier and Their Value to Study the Microbiota-Gut-Brain Axis in Neurodegeneration

We are accumulating evidence that intestinal microflora, collectively named gut microbiota, can alter brain pathophysiology, but researchers have just begun to discover the mechanisms of this bidirectional connection (often referred to as microbiota-gut-brain axis, MGBA). The most noticeable hypothesis for a pathological action of gut microbiota on the brain is based on microbial release of soluble neurotransmitters, hormones, immune molecules and neuroactive metabolites, but this complex scenario requires reliable and controllable tools for its causal demonstration. Thanks to three-dimensional (3D) cultures and microfluidics, engineered in vitro models could improve the scientific knowledge in this field, also from a therapeutic perspective. This review briefly retraces the main discoveries linking the activity of gut microbiota to prevalent brain neurodegenerative disorders, and then provides a deep insight into the state-of-the-art for in vitro modeling of the brain and the blood-brain barrier (BBB), two key players of the MGBA. Several brain and BBB microfluidic devices have already been developed to implement organ-on-a-chip solutions, but some limitations still exist. Future developments of organ-on-a-chip tools to model the MGBA will require an interdisciplinary approach and the synergy with cutting-edge technologies (for instance, bioprinting) to achieve multi-organ platforms and support basic research, also for the development of new therapies against neurodegenerative diseases.
Doxorubicin Induces Endotheliotoxicity and Mitochondrial Dysfunction via ROS/eNOS/NO Pathway

Background: Doxorubicin (Dox) can induce endotheliotoxicity and damage the vascular endothelium (VE). The most principle mechanism might be excess reactive oxygen species (ROS) generation. Nevertheless, the characteristics of ROS generation, downstream mechanisms, and target organelles in Dox-induced endotheliotoxicity have yet to be elucidated. Methods and Results: In order to explore the related problems, the VE injury models were established in mice and human umbilical vein endothelial cells (HUVECs) by Dox-induced endotheliotoxicity. Results showed that the activities of lactate dehydrogenase (LDH) and creatine kinase of mice’s serum increased after injected Dox. The thoracic aortic strips’ endothelium-dependent dilation was significantly impaired, seen noticeable inflammatory changes, and brown TUNEL-positive staining in microscopy. After Dox-treated, HUVECs viability lowered, LDH and caspase-3 activities, and apoptotic cells increased. Both intracellular/mitochondrial ROS generation significantly increased, and intracellular ROS generation lagged behind mitochondria. HUVECs treated with Dox plus ciclosporin A (CsA) could basically terminate ROS burst, but plus edaravone (Eda) could only delay or inhibit, but could not completely cancel ROS burst. Meanwhile, the expression of endothelial nitric oxide synthase (eNOS) decreased, especially phosphorylation of eNOS significantly. Then nitric oxide content decreased, the mitochondrial function was impaired, mitochondrial membrane potential (MMP) impeded, mitochondrial swelled, mitochondrial permeability transition pore (mPTP) was opened, and cytochrome C was released from mitochondria into the cytosol. Conclusion: Dox produces excess ROS in the mitochondria, thereby weakens the MMP, opens mPTP, activates the ROS-induced ROS release mechanism, induces ROS burst, and leads to mitochondrial dysfunction, which in turn damages VE. Therefore, interrupting any step of the cycles, as mentioned above can end the related vicious cycle and prevent the occurrence and development of injury.
Influence of Reaction Parameters on the Catalytic Upgrading of an Acetone, Butanol, and Ethanol (ABE) Mixture: Exploring New Routes for Modern Biorefineries

Here we present a comprehensive study on the effect of reaction parameters on the upgrade of an acetone, butanol and ethanol mixture—key molecules and platform products of great interest within the chemical sector. Using a selected high performing catalyst, Fe/MgO-Al2O3, the variation of temperature, reaction time, catalytic loading, and reactant molar ratio have been examined in this reaction. This work is aiming to not only optimize the reaction conditions previously used, but to step toward using less energy, time, and material by testing those conditions and analyzing the sufficiency of the results. Herein, we demonstrate that this reaction is favored at higher temperatures and longer reaction time. Also, we observe that increasing the catalyst loading had a positive effect on the product yields, while reactant ratios have shown to produce varied results due to the role of each reactant in the complex reaction network. In line with the aim of reducing energy and costs, this work showcases that the products from the upgrading route have significantly higher market value than the reactants; highlighting that this process represents an appealing route to be implemented in modern biorefineries.
Revealing Relationships Among Cognitive Functions Using Functional Connectivity and a Large-Scale Meta-Analysis Database

To characterize each cognitive function per se and to understand the brain as an aggregate of those functions, it is vital to relate dozens of these functions to each other. Knowledge about the relationships among cognitive functions is informative not only for basic neuroscientific research but also for clinical applications and developments of brain-inspired artificial intelligence. In the present study, we propose an exhaustive data mining approach to reveal relationships among cognitive functions based on functional brain mapping and network analysis. We began our analysis with 109 pseudo-activation maps (cognitive function maps; CFM) that were reconstructed from a functional magnetic resonance imaging meta-analysis database, each of which corresponds to one of 109 cognitive functions such as ‘emotion,’ ‘attention,’ ‘episodic memory,’ etc. Based on the resting-state functional connectivity between the CFMs, we mapped the cognitive functions onto a two-dimensional space where the relevant functions were located close to each other, which provided a rough picture of the brain as an aggregate of cognitive functions. Then, we conducted so-called conceptual analysis of cognitive functions using clustering of voxels in each CFM connected to the other 108 CFMs with various strengths. As a result, a CFM for each cognitive function was subdivided into several parts, each of which is strongly associated with some CFMs for a subset of the other cognitive functions, which brought in sub-concepts (i.e., sub-functions) of the cognitive function. Moreover, we conducted network analysis for the network whose nodes were parcels derived from whole-brain parcellation based on the whole-brain voxel-to-CFM resting-state functional connectivities. Since each parcel is characterized by associations with the 109 cognitive functions, network analyses using them are expected to inform about relationships between cognitive and network characteristics. Indeed, we found that informational diversities of interaction between parcels and densities of local connectivity were dependent on the kinds of associated functions. In addition, we identified the homogeneous and inhomogeneous network communities about the associated functions. Altogether, we suggested the effectiveness of our approach in which we fused the large-scale meta-analysis of functional brain mapping with the methods of network neuroscience to investigate the relationships among cognitive functions.
Diversity and Function of Phage Encoded Depolymerases

Bacteriophages of the Podoviridae family often exhibit so-called depolymerases as structural components of the virion. These enzymes appear as tail spike proteins (TSPs). After specific binding to capsular polysaccharides (CPS), exopolysaccharides (EPS) or lipopolysaccharide (LPS) of the host bacteria, polysaccharide-repeating units are specifically cleaved. Finally, the phage reaches the last barrier, the cell wall, injects its DNA, and infects the cell. Recently, similar enzymes from bacteriophages of the Ackermannviridae, Myoviridae, and Siphoviridae families were also described. In this mini-review the diversity and function of phage encoded CPS-, EPS-, and LPS-degrading depolymerases is summarized. The function of the enzymes is described in terms of substrate specificity and applications in biotechnology.