Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella

ABSTRACT Innate-immunity-related genes in humans are activated during urinary tract infections (UTIs) caused by pathogenic strains of Escherichia coli but are suppressed by commensals. Epigenetic mechanisms play a pivotal role in the regulation of gene expression in response to environmental stimuli. To determine whether epigenetic mechanisms can explain the different behaviors of pathogenic and commensal bacteria, we infected larvae of the greater wax moth, Galleria mellonella, a widely used model insect host, with a uropathogenic E. coli (UPEC) strain that causes symptomatic UTIs in humans or a commensal-like strain that causes asymptomatic bacteriuria (ABU). Infection with the UPEC strain (CFT073) was more lethal to larvae than infection with the attenuated ABU strain (83972) due to the recognition of each strain by different Toll-like receptors, ultimately leading to differential DNA/RNA methylation and histone acetylation. We used next-generation sequencing and reverse transcription (RT)-PCR to correlate epigenetic changes with the induction of innate-immunity-related genes. Transcriptomic analysis of G. mellonella larvae infected with E. coli strains CFT073 and 83972 revealed strain-specific variations in the class and expression levels of genes encoding antimicrobial peptides, cytokines, and enzymes controlling DNA methylation and histone acetylation. Our results provide evidence for the differential epigenetic regulation of transcriptional reprogramming by UPEC and ABU strains of E. coli in G. mellonella larvae, which may be relevant to understanding the different behaviors of these bacterial strains in the human urinary tract.
Factors related to Chinese older adults’ suicidal thoughts and attempts

Objectives: Guided by the biopsychosocial framework and empirical evidence, this study examined protective and risk factors of older adults’ suicidal thoughts and attempts during the previous month, 12 months, and 5 years. Method: The data used in this study were extracted from the Sample Survey on Aged Population in Urban/Rural China conducted in 2006, which included 15,957 older adults from mainland China. Multiple penalized logistic regressions were used to conduct the analyses. Results: During the previous month, 12 months, and 5 years, 5.1‰, 10.0‰, and 17.7‰ of older adults indicated that they thought about suicide, whereas 2.2‰, 3.5‰, and 6.3‰ reported suicidal attempts, respectively. Older adults’ age, financial strain, functional limitations, depression, children's filial piety, social network, loneliness, and urban residence were significantly related to suicidal thoughts during the different time periods. In addition, older adults’ religious affiliation, depression, loneliness, and urban residence were significantly related to suicidal attempts during the different time periods. Conclusion: Older adults’ suicidal thoughts and attempts need to be assessed by mental health care professionals and primary care doctors. Programs addressing these important protective and risk factors may help reduce older adults’ suicidal thoughts and attempts.
A Novel M2e Based Flu Vaccine Formulation for Dogs

Background The USA 2004 influenza virus outbreak H3N8 in dogs heralded the emergence of a new disease in this species. A new inactivated H3N8 vaccine was developed to control the spread of the disease but, as in humans and swine, it is anticipated that the virus will mutate shift and drift in the dog population. Therefore, there is a need for a vaccine that can trigger a broad protection to prevent the spread of the virus and the emergence of new strains. Methodology and Principal Findings The universal M2e peptide is identical in almost all the H3N8 influenza strains sequenced to date and known to infect dogs. This epitope is therefore a good choice for development of a vaccine to provide broad protection. Malva mosaic virus (MaMV) nanoparticles were chosen as a vaccine platform to improve the stability of the M2e peptide and increase its immunogenicity in animals. The addition of an adjuvant (OmpC) purified from Salmonella typhi membrane in the vaccine formulation increased the immune response directed to the M2e peptide significantly and enlarged the protection to include the heterosubtypic strain of influenza in a mouse model. An optimal vaccine formulation was also shown to be immunogenic in dogs. Conclusions and Significance The MaMV vaccine platform triggered an improved immune response directed towards the universal M2e peptide. The adjuvant OmpC increased the immune response to the M2e peptide and protection to a heterosubtypic influenza strain that harbors a different M2e peptide in a mouse model. Antibodies generated by the vaccine formulation showed cross-reactivity with M2e peptides derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows a potential for commercialization of a new M2e based vaccine in dogs.
Competitive Interactions of Ligands and Macromolecular Crowders with Maltose Binding Protein

Cellular signaling involves a cascade of recognition events occurring in a complex environment with high concentrations of proteins, polysaccharides, and other macromolecules. The influence of macromolecular crowders on protein binding affinity through hard-core repulsion is well studied, and possible contributions of protein-crowder soft attraction have been implicated recently. Here we present direct evidence for weak association of maltose binding protein (MBP) with a polysaccharide crowder Ficoll, and that this association effectively competes with the binding of the natural ligand, maltose. Titration data over wide ranges of maltose and Ficoll concentrations fit well with a three-state competitive binding model. Broadening of MBP 1H15N TROSY spectra by the addition of Ficoll indicates weak protein-crowder association, and subsequent recovery of sharp NMR peaks upon addition of maltose indicates that the interactions of the crowder and the ligand with MBP are competitive. We hypothesize that, in the Escherichia coli periplasm, the competitive interactions of polysaccharides and maltose with MBP could allow MBP to shuttle between the peptidoglycan attached to the outer membrane and the ATP-binding cassette transporter in the inner membrane.
Rifampicin Nanoprecipitation using Flow Focusing Microfluidic Device

We present the nanoprecipitation of rifampicin performed in a microfluidic device as a means to reduce the particle size and enhance the dissolution rate. The microfluidic device was microfabricated in glass substrate with a 45° flow-focusing geometry. The dimensions of the central and side channels are 100 µm and 110 µm in width, respectively, and 85 µm in depth. We analyze the influence of different parameters in the rifampicin particles size, such as: rifampicin concentration, the presence of surfactant, the total fluid flow and solvent to anti-solvent flow rate ratio. The processed rifampicin was evaluated not only in terms of size, but also morphology, crystallinity, thermal characteristics and dissolution rate. We produce particle sizes in a controlled manner with sizes ranging from 100 nm to 1.2 µm. The particles present an amorphous profile and enhanced dissolution rate as compared to commercial raw rifampicin. These results are promising and have enabled us to better understand the rifampicin self-assembly process in microfluidic device .
Initial consonant deletion in bilingual Spanish–English-speaking children with speech sound disorders

ABSTRACT The purpose of this study was to utilize a theoretical model of bilingual speech sound production as a framework for analyzing the speech of bilingual children with speech sound disorders. In order to distinguish speech difference from speech disorder, we examined between-language interaction on initial consonant deletion, an error pattern found cross-linguistically in the speech of children with speech sound disorders. Thirteen monolingual English-speaking and bilingual Spanish-and English-speaking preschoolers with speech sound disorders were audio-recorded during a single word picture-naming task and their recordings were phonetically transcribed. Initial consonant deletion errors were examined both quantitatively and qualitatively. An analysis of cross-linguistic effects and an analysis of phonemic complexity were performed. Monolingual English-speaking children exhibited initial consonant deletion at a significantly lower rate than bilingual children in their Spanish productions; however, no other quantitative differences were found across groups or languages. Qualitative differences yielded between-language interaction in the error patterns of bilingual children. Phonemic complexity appeared to play a role in initial consonant deletion. Evidence from the speech of bilingual children with speech sound disorders supports analysing bilingual speech using a cross-linguistic framework. Both theoretical and clinical implications are discussed.
Health-Related Quality of Life Among Homeless Smokers: Risk and Protective Factors of Latent Class Membership

ABSTRACT Health-related quality of life (HRQoL) is a multidimensional assessment of well-being and health status. Most work in this area assumes that HRQoL is a homogenous construct; however, it is possible HRQoL subgroups may exist. The purpose of the study was to characterize common classes of HRQoL among adult, homeless smokers, a particularly vulnerable group of the larger population, and to evaluate risk and protective factors of HRQoL class membership. Homeless smokers (N = 456; 65.1% male; Mage = 43.19 years [SD = 11.77]) completed self-report measures of sociodemographics, smoking characteristics, anxiety sensitivity, stress, social support, and the Center for Disease Control (CDC) four-item HRQoL measure. A latent class analysis was conducted for HRQoL. Multinomial regression models were used to simultaneously test correlates of class membership. A three-class solution, consisting of poor HRQoL, moderate HRQoL, and excellent HRQoL, demonstrated superior fit. Correlates of class membership included sex, age, lifetime months of being homeless, smoking characteristics, anxiety sensitivity, stress, and social support. The current findings provide novel evidence for three distinct classes of HRQoL among homeless smokers. Results suggest that older smokers with greater emotional distress, as evidenced by greater anxiety sensitivity, greater stress, and less social support, may be particularly vulnerable to poorer HRQoL.
Species Comparison of Postnatal Development of the Female Reproductive System

The postnatal development of the female reproductive system in laboratory animals and humans is reviewed. To enable a meaningful species comparison of the developing female reproductive system, common definitions of developmental processes were established with a focus made on aspects that are similar across species. A species comparison of the key endocrine, morphologic, and functional (onset of ovarian cycles and ability to reproduce) features of postnatal development of the female reproductive system is provided for human, nonhuman primate, dog, rat, and also mouse, minipig, and rabbit where possible. Species differences in the timing and control of female sexual maturation are highlighted.
Autologous hematopoietic cell transplantation in multiple sclerosis

ABSTRACT Introduction: Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that’s responding poorly to disease modifying therapy. Areas covered: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach. Expert opinion: Currently published data suggest that AHCT’s use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis.
Effects of exposure to nanoparticle-rich diesel exhaust on 8-OHdG synthesis in the mouse asthmatic lung

It has been demonstrated that exposure to diesel exhaust (DE) is associated with the induction and exacerbation of respiratory disorders; however, the impacts of DE containing mainly nanoparticles have been less studied. We have previously demonstrated that inhalation exposure to nanoparticle-rich DE (NR-DE) exacerbated allergic pulmonary inflammation, in the context of enhanced local expression of proinflammatory molecules. However, the underlying mechanisms have not been fully elucidated. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative damage, particularly in DNA. This study examined the effects of NR-DE on 8-OHdG synthesis in the lung in the presence or absence of an allergen. Institute for Cancer Research (ICR) mice were exposed by inhalation to four different gas compositions (control air, low-concentration DE, high-concentration DE and high-concentration DE without particulate matter) for 8 weeks, in the presence or absence of repetitive intratracheal administration of ovalbumin (OVA). Thereafter, we assessed the levels of 8-OHdG synthesis and expression in the lungs by means of enzyme immunoassay (EIA) and immunohistochemistry. The EIA revealed that the level of 8-OHdG was significantly higher in the high-concentration NR-DE-exposed and allergen-sensitized/stimulated group compared with that in the control air-exposed and allergen-treated group. The immunohistochemistry results demonstrated that the level of immunoreactive 8-OHdG was higher in the NR-DE-exposed and allergen-treated lungs compared with that in the corresponding control air-exposed lungs. The results suggested that NR-DE exposure enhanced 8-OHdG formation in asthmatic lungs. This, at least in part, is involved in the NR-DE-mediated exacerbation of the allergic pathophysiology that was identified in our previous study.
Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution.
GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub-population of cancer cells that are endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs could be isolated as high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh cells and investigated the molecular aspects. ALDH1high cells showed greater sphere-forming ability and higher tumor-initiating ability in immune-deficient mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene knockdown by siRNAs decreased the sphere-forming ability and invasion ability, whereas GRIK2 overexpression increased the sphere-forming ability, invasion ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2 and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma cases. The findings indicate that GRIK2 has a role in the maintenance of urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas.
The Android Update Problem: An Empirical Study

Many phone vendors use Android as their underlying OS, but often extend it to add new functionality and to make it compatible with their specific phones. When a new version of Android is released, phone vendors need to merge or re-apply their customizations and changes to the new release. This is a difficult and time-consuming process, which often leads to late adoption of new versions. In this paper, we perform an empirical study to understand the nature of changes that phone vendors make, versus changes made in the original development of Android. By investigating the overlap of different changes, we also determine the possibility of having automated support for merging them. We develop a publicly available tool chain, based on a combination of existing tools, to study such changes and their overlap. As a proxy case study, we analyze the changes in the popular community-based variant of Android, LineageOS, and its corresponding Android versions. We investigate and report the common types of changes that occur in practice. Our findings show that 83% of subsystems modified by LineageOS are also modified in the next release of Android. By taking the nature of overlapping changes into account, we assess the feasibility of having automated tool support to help phone vendors with the Android update problem. Our results show that 56% of the changes in LineageOS have the potential to be safely automated.
Sequence and timing of early cranial skeletal development in Xenopus laevis

Xenopus laevis is widely used as a model organism in biological research. Morphological descriptions of the larval cartilaginous skeleton are more than half a century old and comprehensive studies of early cartilage differentiation and development are missing. A proper understanding of early cranial skeletal development in X. laevis requires a detailed description that can function as a baseline for experimental studies. This basis makes it possible to evaluate skeletal defects produced by experiments on gene interactions, such as gain‐ or loss‐of function experiments. In this study, we provide a detailed description of the pattern and timing of early cartilage differentiation and development in the larval head of X. laevis. Methods used include antibody staining, confocal laser scanning microscopy and 3D‐reconstruction. Results were than compared to earlier studies based on classical histological approaches and clearing‐and‐staining. The first cartilage to chondrify is, in contrast to other vertebrates investigated so far, the ceratohyal. The components of the branchial basket chondrify in anterior‐to‐posterior direction as reported for other amphibians. Chondrification of different cartilages begins at different stages and the majority of cartilages are fully developed at Ziermann and Olsson stage 17. Our baseline data on the pattern and timing of early cartilaginous development in X. laevis is useful for evaluation of experiments which alter head skeletal development as well as for identifying heterochronic shifts in head development in other amphibians.
PHY-layer Fairness in Amplify and Forward Cooperative Diversity Systems

We deal with the concept of physical-layer fairness in amplify and forward cooperative diversity systems, which reflects the need for equally allocating the consumed power among the relays. To this end, we propose a method which utilizes knowledge on both the instantaneous and average channel conditions in order to encompass this concept, by attributing a weight coefficient to each relay depending on its average channel state and then selecting the relay with the best instantaneous "weighted" channel conditions. We also provide a performance analysis of the proposed scheme that includes an analytical expression for the outage probability, together with a closed form one in the high signal-to-noise-ratio (SNR) regime. Through the latter expression, the average symbol error probability (ASEP) for high SNRs is also derived. Numerical results demonstrate that, for small number of available relays or for high SNRs, the performance of the proposed scheme resembles that of the "best relay selection" scheme, in terms of outage probability and ASEP, despite maintaining the average power consumptions equal.
Hierarchical Population Genetic Structure in a Direct Developing Antarctic Marine Invertebrate

Understanding the relationship between life-history variation and population structure in marine invertebrates is not straightforward. This is particularly true of polar species due to the difficulty of obtaining samples and a paucity of genomic resources from which to develop nuclear genetic markers. Such knowledge, however, is essential for understanding how different taxa may respond to climate change in the most rapidly warming regions of the planet. We therefore used over two hundred polymorphic Amplified Fragment Length Polymorphisms (AFLPs) to explore population connectivity at three hierachical spatial scales in the direct developing Antarctic topshell Margarella antarctica. To previously published data from five populations spanning a 1500 km transect along the length of the Western Antarctic Peninsula, we added new AFLP data for four populations separated by up to 6 km within Ryder Bay, Adelaide Island. Overall, we found a nonlinear isolation-by-distance pattern, suggestive of weaker population structure within Ryder Bay than is present over larger spatial scales. Nevertheless, significantly positive F st values were obtained in all but two of ten pairwise population comparisons within the bay following Bonferroni correction for multiple tests. This is in contrast to a previous study of the broadcast spawner Nacella concinna that found no significant genetic differences among several of the same sites. By implication, the topshell's direct-developing lifestyle may constrain its ability to disperse even over relatively small geographic scales.