Miracle-dz/UniFAR-FTUs huggingface dataset:
Contribution of Flagellin Pattern Recognition to Intestinal Inflammation during Salmonella enterica Serotype Typhimurium Infection

ABSTRACT Salmonella enterica serotype Typhimurium causes acute inflammatory diarrhea in humans. Flagella contribute to intestinal inflammation, but the mechanism remains unclear since most mutations abrogating pattern recognition of flagellin also prevent motility and reduce bacterial invasion. To determine the contribution of flagellin pattern recognition to the generation of innate immune responses, we compared in two animal models a nonmotile, but flagellin-expressing and -secreting serotype Typhimurium strain (flgK mutant) to a nonmotile, non-flagellin-expressing strain (flgK fliC fljB mutant). In vitro, caspase-1 can be activated by cytosolic delivery of flagellin, resulting in release of the interferon gamma inducing factor interleukin-18 (IL-18). Experiments with streptomycin-pretreated caspase-1-deficient mice suggested that induction of gamma interferon expression in the murine cecum early (12 h) after serotype Typhimurium infection was caspase-1 dependent but independent of flagellin pattern recognition. In addition, mRNA levels of the CXC chemokines macrophage inflammatory protein 2 and keratinocyte-derived chemokine were markedly increased early after serotype Typhimurium infection of streptomycin-pretreated wild-type mice regardless of flagellin expression. In contrast, in bovine ligated ileal loops, flagellin pattern recognition contributed to increased mRNA levels of macrophage inflammatory protein 3α and more fluid accumulation at 2 h after infection. Collectively, our data suggest that pattern recognition of flagellin contributes to early innate host responses in the bovine ileal mucosa but not in the murine cecal mucosa.
Role of Epidermal Growth Factor Receptor Signaling in the Interaction of Neisseria meningitidis with Endothelial Cells

ABSTRACT Neisseria meningitidis, the causative agent of meningitis and septicemia, attaches to and invades various cell types. Both steps induce and/or require tyrosine phosphorylation of host cell proteins. Here, we used a phospho array platform to identify active receptor tyrosine kinases (RTKs) and key signaling nodes in N. meningitidis-infected brain endothelial cells to decipher RTK-dependent signaling pathways necessary for bacterial uptake. We detected several activated RTKs, including the ErbB family receptors epidermal growth factor receptor (EGFR), ErbB2, and ErbB4. We found that pharmacological inhibition and genetic ablation of ErbB receptor tyrosine phosphorylation and expression resulted in decreased bacterial uptake and heterologous expression of EGFR, ErbB2, or ErbB4 in Chinese ovary hamster (CHO-K1) cells, which do not express of EGFR and ErbB4; the decrease caused a significant increase in meningococcal invasion. Activation of EGFR and ErbB4 was mediated by transactivation via the common ligand HB-EGF (heparin-binding EGF-like ligand), which was significantly elevated in infected cell culture supernatants. We furthermore determined that N. meningitidis induced phosphorylation of EGFR at Tyr845 independent of ligand binding, which required c-Src activation and was involved in mediating uptake of N. meningitidis into eukaryotic cells. Increased uptake was repressed by expression of EGFR Y845F, which harbored a point mutation in the kinase domain. In addition, activation of ErbB4 at its autophosphorylation site, Tyr1284, and phosphorylation of ErbB2 Thr686 were observed. Altogether, our results provide evidence that EGFR, ErbB2, and ErbB4 are activated in response to N. meningitidis infection and shed new light on the role of ErbB signaling in meningococcal infection biology.
Toward the prevention of human birth defects: a personal perspective

ABSTRACT Twenty years ago, the late Professor Hideo Nishimura identified some unsolved problems in teratology. His prediction concerning the future advances in this research area has in part become a reality by the year of 2001, but some difficult problems have still to be solved. We neither understand the causes and initiating mechanisms of a vast majority of birth defects nor have measures that can effectively prevent the birth of malformed babies. With the remarkable advances in molecular biology, the tune has come when we have the ability to elucidate the mechanisms of abnormal development and identify procedures to prevent human birth defects.
Numerical Optimal Control for Problems with Random Forced SPDE Constraints

A numerical algorithm for solving optimization problems with stochastic diffusion equation as a constraint is proposed. First, separation of random and deterministic variables is done via Karhunen-Loeve expansion. Then, the problem is discretized, in spatial part, using the finite element method and the polynomial chaos expansion in the stochastic part of the problem. This process leads to the optimal control problem with a large scale system in its constraint. To overcome these difficulties the adjoint technique for derivative computation to implementation of the optimal control issue in preconditioned Newton’s conjugate gradient method is used. By some numerical simulation, it is shown that this hybrid approach is efficient and simple to implement.
Participation in Out-of-Home Environments for Young Children With and Without Developmental Disabilities

This study examines caregivers’ perceptions of participation patterns and environmental supports and barriers for young children with and without developmental disabilities within their child care/preschool and community settings. The Young Children’s Participation and Environment Measure (YC-PEM) was completed by 151 parents of Singaporean children (0-7 years old) with and without developmental disabilities. Setting-specific summary and item-level scores of these children were compared using ANCOVA, Mann–Whitney U, and Pearson chi-square tests. Children with developmental disabilities had significantly lower participation and environment summary scores in both settings as compared with children without developmental disabilities (p < .05; η p 2 = 0.03-0.31). Group differences were also evident at the item level, particularly when comparing the percentage of parents who desire change in their child’s activity participation. Adequate financial support, public awareness, programs, and services have been identified as environmental factors that are potentially important to parents of children with developmental disabilities.
Putative Inv Is Essential for Basolateral Invasion of Caco-2 Cells and Acts Synergistically with OmpA To Affect In Vitro and In Vivo Virulence of Cronobacter sakazakii ATCC 29544

ABSTRACT Cronobacter sakazakii is an opportunistic pathogen that causes neonatal meningitis and necrotizing enterocolitis. Its interaction with intestinal epithelium is important in the pathogenesis of enteric infections. In this study, we investigated the involvement of the inv gene in the virulence of C. sakazakii ATCC 29544 in vitro and in vivo. Sequence analysis of C. sakazakii ATCC 29544 inv revealed that it is different from other C. sakazakii isolates. In various cell culture models, an Δinv deletion mutant showed significantly lowered invasion efficiency, which was restored upon genetic complementation. Studying invasion potentials using tight-junction-disrupted Caco-2 cells suggested that the inv gene product mediates basolateral invasion of C. sakazakii ATCC 29544. In addition, comparison of invasion potentials of double mutant (ΔompA Δinv) and single mutants (ΔompA and Δinv) provided evidence for an additive effect of the two putative outer membrane proteins. Finally, the importance of inv and the additive effect of putative Inv and OmpA were also proven in an in vivo rat pup model. This report is the first to demonstrate two proteins working synergistically in vitro, as well as in vivo in C. sakazakii pathogenesis.
Fungal Morphogenetic Pathways Are Required for the Hallmark Inflammatory Response during Candida albicans Vaginitis

ABSTRACT Vulvovaginal candidiasis, caused primarily by Candida albicans, presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability of C. albicans to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria for defining vaginitis immunopathology, the purpose of this study was to determine whether the yeast-to-hypha transition is required for the hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses of vaginal infection with C. albicans in C57BL/6 mice demonstrated that fungal burdens remained constant throughout the observation period, while polymorphonuclear leukocyte (PMN), S100A8, and interleukin-1β levels obtained from vaginal lavage fluid increased by day 3 onward. Lactate dehydrogenase activity was also positively correlated with increased effectors of innate immunity. Additionally, immunodepletion of neutrophils in infected mice confirmed a nonprotective role for PMNs during vaginitis. Determination of the importance of fungal morphogenesis during vaginitis was addressed with a two-pronged approach. Intravaginal inoculation of mice with C. albicans strains deleted for key transcriptional regulators (bcr1Δ/Δ, efg1Δ/Δ, cph1Δ/Δ, and efg1Δ/Δ cph1Δ/Δ) controlling the yeast-to-hypha switch revealed a crucial role for morphogenetic signaling through the Efg1 and, to a lesser extent, the Bcr1 pathways in contributing to vaginitis immunopathology. Furthermore, overexpression of transcription factors NRG1 and UME6, to maintain yeast and hyphal morphologies, respectively, confirmed the importance of morphogenesis in generating innate immune responses in vivo. These results highlight the yeast-to-hypha switch and the associated morphogenetic response as important virulence components for the immunopathogenesis of Candida vaginitis, with implications for transition from benign colonization to symptomatic infection.
On the impact of adjacent channel interference in multi-channel VANETs

The efficient usage of multiple channels allocated for vehicular communications is deemed crucial to support the increasing spectrum demand of current and upcoming Intelligent Transportation Systems (ITS). In this context, an accurate modeling of adjacent channel interference (ACI) is needed to better understand its adverse effects on simultaneous communications on different channels. In this paper, we modeled ACI in the simulation framework Veins by strictly following the standard specifications in what concerns spectral emission masks. The model was validated in a set of experiments using off-the-shelf chipsets and a software defined radio. We then studied ACI effects at the physical and packet levels in multi-channel vehicular networks through extensive simulations. Our results clearly indicate that slightly larger delays and significantly lower reliability can be experienced when ACI is modeled. Insights are also provided about the usability of the devised ACI simulation model in future studies.
Building suspiciousness cascading graph over multiple hosts for detecting targeted attacks

In this paper, we propose a novel approach to detect a targeted attack by visualizing the paths of lateral movement in which the attacker compromises several hosts in the targeted network step by step to achieve his final goal. To this end, we first identify a pair of hosts that has a relationship in which a host can have compromised the other host based on the suspiciousness of their activities and communication patterns between them. Then we cluster such pairs as a graph visualizing an attack path. The attack is finally detected based on the graph size. Since this approach is agnostic to specific signatures, it can cope with a wide variety of attacks. The evaluation experiments show our approach achieves both the high detection rate of 97%, and the low false positives, which is 10% of an existing approach.
Replication-competent viruses for cancer therapy

Most cases of cancer, when detected at an advanced stage, cannot be cured with conventional therapeutic modalities. Therefore, novel approaches such as gene therapy are needed. Neverthelass, while the safety record of gene therapy, for cancer has been excellent, clinical efficacy has been limited. Moreover, it has become evident that clinical efficacy is directly determined by gene delivery efficacy. For this reason, the use of replication-competent oncolytic viruses has been proposed. Oncolytic viruses are potentially attractive therapeutics for cancer because they selectively amplify the input treatment dose in target cells Both naturally occurring and genetically engineered oncolytic viruses have been described. The most advanced clinical results are sported for conditionally replicating adenoviruses (CRAds). In this review, we will describe the use of oncolytic viruses as single-agent and combination treatments for cancer.
The Feagaiga and Faife’au ‘Kids’ (FKs): An Examination of the Experiences of Parsonage Children of the Samoan Congregational Denomination in New Zealand

This article examines the experiences of faife’au ‘kids’ (clergy children) of the Samoan Congregational Christian Church denomination in New Zealand. The paper investigates the effects the indigenous concept of feagaiga (covenant) has on faife’au kids (FKs) parsonage experiences. Additionally, the Eurocentric concept of ‘tagata’ese’ (stranger) is also investigated. As part of a master’s research study, Talanoa sessions were conducted with eight FKs of the Congregational denomination in New Zealand. Participants were mainly from the Wellington and Auckland regions.
Multi-stratum resources optimization for cloud-based radio over optical fiber networks

Cloud radio access network (C-RAN) has become a promising scenario to accommodate high-performance services with ubiquitous user coverage and real-time cloud computing using cloud BBUs. In this paper, we propose a novel multistratum resources optimization (MSRO) architecture for cloud-based radio over optical fiber networks with software defined networking. Additionally, a global evaluation strategy (GES) is introduced in the proposed architecture. The MSRO can enhance the responsiveness to end-to-end user demands and globally optimize radio frequency, optical spectrum and BBU processing resources effectively to maximize radio coverage. The overall feasibility and efficiency of the proposed architecture with GES strategy are experimentally verified on OpenFlow-enabled testbed in terms of resource occupation rate and path provisioning latency.
Sortase A Utilizes an Ancillary Protein Anchor for Efficient Cell Wall Anchoring of Pili in Streptococcus agalactiae

ABSTRACT Pili are putative virulence factors and promising vaccine candidates in Streptococcus agalactiae (group B Streptococcus [GBS]) infection, a leading cause of neonatal sepsis and meningitis. The genes necessary for pilus synthesis and assembly are clustered in pilus islands (PI). Each gene encodes three structural subunits (a backbone and two ancillary proteins) bearing a C-terminal LPXTG motif and two subfamily C sortases (SrtC) involved in covalent polymerization of the subunits. GBS strains also possess the conserved “housekeeping” sortase A (SrtA), but its role in pilus assembly is unclear. To address this issue, pilus expression and cell wall anchoring were analyzed in srtA deletion mutants. Loss of SrtA did not affect pilus polymerization. However, pilus expression on the cell surface was reduced, and pili accumulated in the culture supernatant. Furthermore, cell-associated pili could be readily released by detergent treatment, indicating that SrtA is involved in covalent anchoring of pili to the cell wall. When each of the genes comprising PI-2a was systematically deleted, only the absence of ancillary subunit GBS150 or the SrtC required for incorporation of GBS150 into pili mimicked the srtA mutant phenotype. Thus, from these data a model for GBS pilus assembly can be proposed in which PI sortases are responsible for polymerization of the pilus structure, while SrtA is required to covalently attach it to the cell wall, utilizing ancillary pilus subunit GBS150 as the anchor protein.
Ergodic secrecy capacity analysis for cooperative communication with relay selection under non-identical distribution

In this paper, ergodic secrecy capacity is analyzed in a cooperative communication network, for an independent but non-identically distributed (i.n.i.d) Rayleigh fading channel. By using multi-trusted decode and forward relays, the model assumes direct links between a sender (Alice) and receiver nodes (Bob and an eavesdropper); in addition both Alice and the relay have perfect knowledge about the eavesdropper's channel state information (CSI). The protocol employed herein selects the best relay with the highest signal-to-noise ratio (SNR) in relation to the destination (Bob), while maximum ratio combining (MRC) is employed at Bob and the eavesdropper's terminals. Finally, the theoretical analysis is validated through simulation, and the results show that performance is enhanced with an increasing number of relays, in the event of a direct link between the sender and the receiver's terminals.
A Novel Chimeric Plasmodium vivax Circumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

ABSTRACT A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel “immunologically optimal” recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses.
Gastric De Novo Muc13 Expression and Spasmolytic Polypeptide-Expressing Metaplasia during Helicobacter heilmannii Infection

ABSTRACT Helicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H+/K+-ATPase α/β and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.
A spatiotemporal model for the LTE uplink: Spatially interacting tandem queues approach

With the proliferation of the Internet-of-things (IoT), there is an undeniable consensus that cellular LTE networks will have to support a dramatically larger number of uplink connections. This is true since most of the devices to be added incur machine-type communications which is dominantly upstream. Can current LTE network withstand this challenge? To answer this question, the joint performance of random access process and the uplink data transmission should be investigated. These two problems have been classically treated in the literature in a disjoint fashion. In this paper, they are jointly analyzed as an inseparable couple. To do that, a tandem queuing model is adopted whereby devices are represented as spatially interacting queues. The interaction between queues is governed by the mutual inter-cell and intra-cell interference. To that end, a joint stochastic geometry and queueing theory model is exploited to study this problem and a spatiotemporal analytical model is developed accordingly. Network stability and scalability are two prime performance criteria for performance assessment. In light of these two criteria, the developed model is poised to offer valuable insights into efficient access and resource allocation strategies.
Streptococcus pneumoniae ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation

ABSTRACT Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.