At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence ...factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in
Pseudomonas aeruginosa
. Our results show that
trans
-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in
P. aeruginosa
PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the
las
and
rhl
QS systems with
lasI
and
lasR
levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in
P. aeruginosa
.
The spread of novel virus SARS‐CoV‐2, well known as COVID‐19 has become a major health issue currently which has turned up to a pandemic worldwide. The treatment recommendations are variable. Lack of ...appropriate medication has worsened the disease. On the basis of prior research, scientists are testing drugs based on medical therapies for SARS and MERS. Many drugs which include lopinavir, ritonavir and thalidomide are listed in the new recommendations. A topological index is a type of molecular descriptor that simply defines numerical values associated with the molecular structure of a compound that is effectively used in modeling many physicochemical properties in numerous quantitative structure–property/activity relationship (QSPR/QSAR) studies. In this study, several degree‐based and neighborhood degree sum‐based topological indices for several antiviral drugs were investigated by using a M‐polynomial and neighborhood M‐polynomial methods. In addition, a QSPR was established between the various topological indices and various physicochemical properties of these antiviral drugs along with remdesivir, chloroquine, hydroxychloroquine and theaflavin was performed in order to assess the efficacy of the calculated topological indices. The obtained results reveal that topological indices under study have strong correlation with the physicochemical characteristics of the potential antiviral drugs. A biological activity (pIC50) of these compounds were also investigated by using multiple linear regressions (MLR) analysis.
The main results of this paper are several degree based and neighborhood degree based topological indices of antiviral drugs for the treatment of COVID‐19 like Lopinavir, Ritonavir, Arbidol and Thalidomide through M‐polynomial and NM‐polynomial by analyzing their molecular structures. Moreover it establishes a strong correlation between physicochemical properties of antiviral drugs and the topological indices tested.
Despite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Additionally, relationships between the responding cell type and ...nanomaterial properties are not well understood. Using three model cell lines representing different physiological compartments and nanomaterials of different compositions and sizes, we have systematically investigated the influence of nanomaterial properties on the degrees and pathways of cytotoxicity. In this study, we selected nanomaterials of different compositions (TiO2 and SiO2 nanoparticles, and multi-wall carbon nanotubes MWCNTs) with differing size (MWCNTs of different diameters < 8 nm, 20-30 nm, > 50 nm; but same length 0.5-2 microm) to analyze the effects of composition and size on toxicity to 3T3 fibroblasts, RAW 264.7 macrophages, and telomerase-immortalized (hT) bronchiolar epithelial cells.
Following characterization of nanomaterial properties in PBS and serum containing solutions, cells were exposed to nanomaterials of differing compositions and sizes, with cytotoxicity monitored through reduction in mitochondrial activity. In addition to cytotoxicity, the cellular response to nanomaterials was characterized by quantifying generation of reactive oxygen species, lysosomal membrane destabilization and mitochondrial permeability. The effect of these responses on cellular fate - apoptosis or necrosis - was then analyzed. Nanomaterial toxicity was variable based on exposed cell type and dependent on nanomaterial composition and size. In addition, nanomaterial exposure led to cell type dependent intracellular responses resulting in unique breakdown of cellular functions for each nanomaterial: cell combination.
Nanomaterials induce cell specific responses resulting in variable toxicity and subsequent cell fate based on the type of exposed cell. Our results indicate that the composition and size of nanomaterials as well as the target cell type are critical determinants of intracellular responses, degree of cytotoxicity and potential mechanisms of toxicity.
Staphylococcus aureus is an opportunistic pathogen that colonizes the skin and mucosal surfaces of mammals. Persistent staphylococcal infections often involve surface-associated communities called ...biofilms. Here we report the discovery of a novel extracellular fibril structure that promotes S. aureus biofilm integrity. Biochemical and genetic analysis has revealed that these fibers have amyloid-like properties and consist of small peptides called phenol soluble modulins (PSMs). Mutants unable to produce PSMs were susceptible to biofilm disassembly by matrix degrading enzymes and mechanical stress. Previous work has associated PSMs with biofilm disassembly, and we present data showing that soluble PSM peptides disperse biofilms while polymerized peptides do not. This work suggests the PSMs' aggregation into amyloid fibers modulates their biological activity and role in biofilms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article presents an analytical model for enhancement-mode GaN devices for high-power application. The model is developed specifically for a GaN gate injection transistor (GIT) device in which a ...positive threshold voltage is achieved by inserting a p-type GaN layer underneath the gate electrode that is incorporated in the analytical model presented in this article. In addition, the operation of enhancement-mode GaN transistors for high-power application is significantly impacted by carrier spill-over at higher gate bias. Therefore, this model also includes the impact of carrier spill-over by considering parallel conduction in the barrier layer adjacent to the two-dimensional electron gas (2DEG) channel of the transistor and the degradation of mobility and charge density on device operation. In addition, due to high power dissipation and low thermal conductivity of GaN material, the device performance degrades at high temperature. In this article, high-temperature operation of the device is modeled by taking into account the temperature exponents of the device parameters that vary with temperature. At high current density, the device shows significant self-heating effect, which is also modeled using a similar approach. The overall model is compared with the experimentally measured data that shows an excellent match.
'Expressed Emotion (EE)' captures ways in which emotions are expressed within a family environment. Research has found that EE in families has an impact on psychiatric illness, in particular ...psychosis, such that it increases risk of relapse. EE was conceptualised by research conducted in the UK. Thus, behaviours defined as pathological were largely based on white samples adhering to UK norms. Cross-cultural variations have been found in EE and its relationship with clinical outcomes. A more culturally appropriate understanding of norms surrounding the EE across cultures is required. This study aims to use a bottom-up approach to provide a culturally specific understanding of family relationships and EE across 'non-clinical' UK-based South Asian families. Semi-structured interviews were conducted with 18 South Asian participants to explore their relationships with a significant other. Interviews were analysed using thematic analysis. Four main themes were generated: expression of love, setting boundaries, inter-generational differences and acceptance. The findings indicate considerable cultural variability within EE and highlight the need to interpret EE in the context of socio-cultural norms. Whilst certain domains of EE that are considered pathological in Western contexts are present in the UK-based South Asian diaspora, these are perceived as less problematic, indicative of varying cultural norms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The 15q11.2 BP1-BP2 microdeletion (Burnside–Butler) syndrome is emerging as the most frequent pathogenic copy number variation (CNV) in humans associated with neurodevelopmental disorders with ...changes in brain morphology, behavior, and cognition. In this study, we explored functions and interactions of the four protein-coding genes in this region, namely NIPA1, NIPA2, CYFIP1, and TUBGCP5, and elucidate their role, in solo and in concert, in the causation of neurodevelopmental disorders. First, we investigated the STRING protein-protein interactions encompassing all four genes and ascertained their predicted Gene Ontology (GO) functions, such as biological processes involved in their interactions, pathways and molecular functions. These include magnesium ion transport molecular function, regulation of axonogenesis and axon extension, regulation and production of bone morphogenetic protein and regulation of cellular growth and development. We gathered a list of significantly associated cardinal maladies for each gene from searchable genomic disease websites, namely MalaCards.org: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards.org. Through tabulations of such disease data, we ascertained the cardinal disease association of each gene, as well as their expanded putative disease associations. This enabled further tabulation of disease data to ascertain the role of each gene in the top ten overlapping significant neurodevelopmental disorders among the disease association data sets: (1) Prader–Willi Syndrome (PWS); (2) Angelman Syndrome (AS); (3) 15q11.2 Deletion Syndrome with Attention Deficit Hyperactive Disorder & Learning Disability; (4) Autism Spectrum Disorder (ASD); (5) Schizophrenia; (6) Epilepsy; (7) Down Syndrome; (8) Microcephaly; (9) Developmental Disorder, and (10) Peripheral Nervous System Disease. The cardinal disease associations for each of the four contiguous 15q11.2 BP1-BP2 genes are NIPA1- Spastic Paraplegia 6; NIPA2—Angelman Syndrome and Prader–Willi Syndrome; CYFIP1—Fragile X Syndrome and Autism; TUBGCP5—Prader–Willi Syndrome. The four genes are individually associated with PWS, ASD, schizophrenia, epilepsy, and Down syndrome. Except for TUBGCP5, the other three genes are associated with AS. Unlike the other genes, TUBGCP5 is also not associated with attention deficit hyperactivity disorder and learning disability, developmental disorder, or peripheral nervous system disease. CYFIP1 was the only gene not associated with microcephaly but was the only gene associated with developmental disorders. Collectively, all four genes were associated with up to three-fourths of the ten overlapping neurodevelopmental disorders and are deleted in this most prevalent known pathogenic copy number variation now recognized among humans with these clinical findings.
This paper studies various forms of analytical solutions for mixed derivative nonlinear Schrödinger equation (MD-NLSE) which is used extensively in optical fiber. Our aim is to obtain lump solution ...(which is analytic in all directions), lump with one kink, rogue waves, periodic waves and multi-wave solutions for our governing model. We also discuss the interaction between periodic and lump, breather wave (which is a localized periodic wave solution of either discrete lattice or continuous media mathematical models), generalized breather, Ma-breather, Kuznetsov-Ma-breather and their corresponding rogue waves. At the end, we also present the dynamical behaviour of our solutions in terms of graphs in various dimensions.
The 15q11.2 BP1-BP2 microdeletion (
) syndrome is emerging as the most frequent pathogenic copy number variation (CNV) in humans associated with neurodevelopmental disorders with changes in brain ...morphology, behavior, and cognition. In this study, we explored functions and interactions of the four protein-coding genes in this region, namely
,
,
, and
, and elucidate their role, in solo and in concert, in the causation of neurodevelopmental disorders. First, we investigated the STRING protein-protein interactions encompassing all four genes and ascertained their predicted Gene Ontology (GO) functions, such as biological processes involved in their interactions, pathways and molecular functions. These include magnesium ion transport molecular function, regulation of axonogenesis and axon extension, regulation and production of bone morphogenetic protein and regulation of cellular growth and development. We gathered a list of significantly associated cardinal maladies for each gene from searchable genomic disease websites, namely MalaCards.org: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards.org. Through tabulations of such disease data, we ascertained the cardinal disease association of each gene, as well as their expanded putative disease associations. This enabled further tabulation of disease data to ascertain the role of each gene in the top ten overlapping significant neurodevelopmental disorders among the disease association data sets: (1) Prader-Willi Syndrome (PWS); (2) Angelman Syndrome (AS); (3) 15q11.2 Deletion Syndrome with Attention Deficit Hyperactive Disorder & Learning Disability; (4) Autism Spectrum Disorder (ASD); (5) Schizophrenia; (6) Epilepsy; (7) Down Syndrome; (8) Microcephaly; (9) Developmental Disorder, and (10) Peripheral Nervous System Disease. The cardinal disease associations for each of the four contiguous 15q11.2 BP1-BP2 genes are
- Spastic Paraplegia 6;
-Angelman Syndrome and Prader-Willi Syndrome;
-Fragile X Syndrome and Autism;
-Prader-Willi Syndrome. The four genes are individually associated with PWS, ASD, schizophrenia, epilepsy, and Down syndrome. Except for
, the other three genes are associated with AS. Unlike the other genes,
is also not associated with attention deficit hyperactivity disorder and learning disability, developmental disorder, or peripheral nervous system disease.
was the only gene not associated with microcephaly but was the only gene associated with developmental disorders. Collectively, all four genes were associated with up to three-fourths of the ten overlapping neurodevelopmental disorders and are deleted in this most prevalent known pathogenic copy number variation now recognized among humans with these clinical findings.
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