Cotton textiles are ubiquitous in daily life and are also one of the primary mediums for transmitting viruses and bacteria. Conventional approaches to fabricating antiviral and antibacterial textiles ...generally load functional additives onto the surface of the fabric and/or their microfibres. However, such modifications are susceptible to deterioration after long-term use due to leaching of the additives. Here we show a different method to impregnate copper ions into the cellulose matrix to form a copper ion-textile (Cu-IT), in which the copper ions strongly coordinate with the oxygen-containing polar functional groups (for example, hydroxyl) of the cellulose chains. The Cu-IT displays high antiviral and antibacterial performance against tobacco mosaic virus and influenza A virus, and Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa and Bacillus subtilis bacteria due to the antimicrobial properties of copper. Furthermore, the strong coordination bonding of copper ions with the hydroxyl functionalities endows the Cu-IT with excellent air/water retainability and superior mechanical stability, which can meet daily use and resist repeated washing. This method to fabricate Cu-IT is cost-effective, ecofriendly and highly scalable, and this textile appears very promising for use in household products, public facilities and medical settings.
Molecular characterization of avian pathogenic Escherichia coli (APEC) is challenging due to the complex nature of its associated disease, colibacillosis, in poultry. Numerous efforts have been made ...toward defining APEC, and it is becoming clear that certain clonal backgrounds are predictive of an avian E. coli isolate's virulence potential. Thus, APEC can be further differentiated as high-risk APEC based upon their clonal background's virulence potential. However, less clear is the degree of overlap between clinical isolates of differing bird type, and between clinical and gastrointestinal isolates. This study aimed to determine genomic similarities and differences between such populations, comparing commercial broiler vs. turkey isolates, and clinical vs. gastrointestinal isolates. Differences were observed in Clermont phylogenetic groups between isolate populations, with B2 as the dominant group in turkey clinical isolates and G as the dominant group in broiler clinical isolates. Nearly all clinical isolates were classified as APEC using a traditional gene-based typing scheme, whereas 53.4% and 44.1% of broiler and turkey gastrointestinal isolates were classified as APEC, respectively. High-risk APEC were identified among 31.0% and 46.9% of broiler and turkey clinical isolates, compared with 5.7% and 2.9% of broiler and turkey gastrointestinal isolates. As found in previous studies, no specific known virulence or fitness gene sets were identified which universally differentiate between clinical and gastrointestinal isolates. This study further demonstrates the utility of a hybrid APEC typing approach, considering both plasmid content and clonal background, for the identification of dominant and highly virulent APEC clones in poultry production.
The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system ...is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens-and especially intracellular bacteria-by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
Osteogenesis imperfecta (OI) is a genetic disease commonly caused by mutations in the COL1A1 or COL1A2 gene affecting the production of type I collagen, a major component of bone that determines the ...toughness of bone, or its resistance to fracture. Thus, patients with OI present with brittle bones and higher rates of skeletal fractures. Additionally, defects in the collagen framework of developing bones impair their biomineralization, further compromising bone mechanical properties. Previous work in our lab investigated BMD at cranial locations which experience compressive forces during feeding (e.g. joints). Muscles also contribute to cranial growth through tensile forces exerted on bone during contraction, but the relationship between muscle function and bone quality in OI is unclear. The aim of this study is to quantify the BMD in a mouse model of OI, with a focus on skeletal sites associated with cranial musculature. We hypothesize that the mice with OI will have lower BMD in skeletal areas associated with muscle attachment compared to their unaffected littermates.
To test our hypothesis, we used the homozygous recessive OI murine (OIM) mouse (B6C3Fe a/a‐Col1a2oim/J), a model for the severe type III OI seen in humans. Adult (16 weeks old) OIM mice (n=11) and wildtype (WT, n=13) littermates were CT scanned, and BMD was measured using the Bruker CTAnalyzer software in 7 regions of interest encompassing muscle attachment sites on the mandible, zygomatic arch, and parietal bone. For each region, BMD values were compared between genotypes by a Kruskal‐Wallis test.
OI mice had significantly lower BMD at the coronoid process (p=0.007), parietal bone (p=0.031), and posterior mylohyoid line (p=0.007) compared to WT mice. No significant differences were found in BMD at the gonial angle or zygomatic arch. This suggests a disproportionate weakness of the temporalis and mylohyoid muscles in mice with OI, but not in the masseter muscle. While type I collagen defects impact the structural organization of skeletal muscle, it is possible that masseter muscle function is preserved in OIM mice because of its key roles in rodent feeding and postural control of the jaw. The imbalance between temporalis and masseter muscles may contribute to the prevalence of dental malocclusions in human patients with type III OI.
The findings of this study support further exploration of specific muscle groups (e.g. jaw adductors/temporalis, hyoid muscles/mylohyoid) and efforts to improve their functions during feeding, as a way of recovering facial growth and preventing dental malocclusions in OI. A better appreciation of muscle‐bone interactions in the skull and their effect on bone quality can potentially be used to inform oro‐motor therapies to improve feeding function, muscle strength, and facial bone quality for patients with OI.
Although 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in ovarian cancer, we investigated if ...estrogen regulates MAPK and if MEK inhibition (MEKi) reverses antiestrogen resistance.
Effects of MEKi (selumetinib), antiestrogen (fulvestrant), or both were assayed in ER-positive HGSOC in vitro and in xenografts. Response biomarkers were investigated by gene expression microarray and reverse phase protein array (RPPA). Genes differentially expressed in two independent primary HGSOC datasets with high versus low pMAPK by RPPA were used to generate a "MAPK-activated gene signature." Gene signature components that were reversed by MEKi were then identified.
High intratumor pMAPK independently predicts decreased survival (HR, 1.7; CI > 95%,1.3-2.2; P = 0.0009) in 408 HGSOC from The Cancer Genome Atlas. A differentially expressed "MAPK-activated" gene subset was also prognostic. "MAPK-activated genes" in HGSOC differ from those in breast cancer. Combined MEK and ER blockade showed greater antitumor effects in xenografts than monotherapy. Gene set enrichment analysis and RPPA showed that dual therapy downregulated DNA replication and cell-cycle drivers, and upregulated lysosomal gene sets. Selumetinib reversed expression of a subset of "MAPK-activated genes" in vitro and/or in xenografts. Three of these genes were prognostic for poor survival (P = 0.000265) and warrant testing as a signature predictive of MEKi response.
High pMAPK is independently prognostic and may underlie antiestrogen failure. Data support further evaluation of fulvestrant and selumetinib in ER-positive HGSOC. The MAPK-activated HGSOC signature may help identify MEK inhibitor responsive tumors.
Iron scavenging is required for full virulence of mycobacterial pathogens. During infection, the host immune response restricts mycobacterial access to iron, which is essential for bacterial ...respiration and DNA synthesis. The Mycobacterium tuberculosis iron-dependent regulator (IdeR) responds to changes in iron accessibility by repressing iron-uptake genes when iron is available. In contrast, iron-uptake gene transcription is induced when iron is depleted. The ideR gene is essential in M. tuberculosis and is required for bacterial growth. To further study how iron regulates transcription, wee developed an iron responsive reporter system that relies on an IdeR-regulated promoter to drive Cre and loxP mediated recombination in Mycobacterium smegmatis. Recombination leads to the expression of an antibiotic resistance gene so that mutations that activate the IdeR-regulated promoter can be selected. A transposon library in the background of this reporter system was exposed to media containing iron and hemin, and this resulted in the selection of mutants in the antioxidant mycothiol synthesis pathway. We validated that inactivation of the mycothiol synthesis gene mshA results in increased recombination and increased IdeR-regulated promoter activity in the reporter system. Further, we show that vitamin C, which has been shown to oxidize iron through the Fenton reaction, can decrease promoter activity in the mshA mutant. We conclude that the intracellular redox state balanced by mycothiol can alter IdeR activity in the presence of iron.IMPORTANCEMycobacterium smegmatis is a tractable organism to study mycobacterial gene regulation. We used M. smegmatis to construct a novel recombination-based reporter system that allows for the selection of mutations that deregulate a promoter of interest. Transposon mutagenesis and insertion sequencing (TnSeq) in the recombination reporter strain identified genes that impact iron regulated promoter activity in mycobacteria. We found that the mycothiol synthesis gene mshA is required for IdeR mediated transcriptional regulation by maintaining intracellular redox balance. By affecting the oxidative state of the intracellular environment, mycothiol can modulate iron-dependent transcriptional activity. Taken more broadly, this novel reporter system can be used in combination with transposon mutagenesis to identify genes that are required by Mycobacterium tuberculosis to overcome temporary or local changes in iron availability during infection.
Outfitting an aza-crown ether with an organotransition-metal pendant provides a mechanism for tuning its supramolecular properties. The binding affinity can be tuned by more than 2 orders of ...magnitude by changing the identity of the transition metal-center, altering the overall charge of the complex, or engaging in organometallic ligand substitution reactions. High Li+ selectivity (up to 29-fold higher affinity in comparison to Na+), proton-responsive behavior, and ion pair (ditopic) binding capabilities are observed in the metalla-crown ethers.
A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported, mediated by iridium(
i
) complexes supported by ...aminophenylphosphinite (NCOP) pincer ligands. The decarbonylation, which involves the cleavage of one C-C bond, one C-O bond, and two C-H bonds, along with formation of two new C-H bonds, was serendipitously discovered upon dehydrochlorination of an iridium(
iii
) complex containing an aza-18-crown-6 ether macrocycle. Intramolecular cleavage of macrocyclic and acyclic ethers was also found in analogous complexes featuring aza-15-crown-5 ether or bis(2-methoxyethyl)amino groups. Intermolecular decarbonylation of cyclic and linear ethers was observed when diethylaminophenylphosphinite iridium(
i
) dinitrogen or norbornene complexes were employed. Mechanistic studies reveal the nature of key intermediates along a pathway involving initial iridium(
i
)-mediated double C-H bond activation.
A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported.
More openly sexually and gender diverse people are aging into later life across the world as generational transitions occur. People identifying many different ways beyond cisgender and heterosexual ...are diverse with respect to many other characteristics and sociopolitical locations across the globe and may thus experience a wide array of health journeys both individually and as partners in intimate relationships. In this review article, we summarize the major contributions of and ongoing gaps in existing studies about such couples’ experiences of chronic disease management in later life. We focus on three key groups of findings from prior research about the health of older sexually and/or gender diverse couples: care practices, unmet needs, and diverse resources. We outline priorities for future research within and across these topic areas and in varied locations, with unique recommendations for scholars in both academic and clinical settings. These recommendations support greater integration of such populations, topics, and needs in existing discourse on aging and late life. Likewise, recommendations from this review illuminate potential best practices for engaging and serving these elders in both academic and applied settings.
PDF
