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These results indicate that counteracting PKR is mechanistically different in two species of adenoviruses. IMPORTANCE Viruses have evolved to counteract the immune system to successfully replicate in the host. Downregulation of several antiviral proteins is important for productive viral infection. Protein kinase R (PKR) is an antiviral protein that belongs to the first line of defense of the host. Because PKR senses dsRNA and blocks the cellular translation process during viral infections, it is not surprising that many viruses counteract this antiviral activity. We previously reported PKR degradation during mouse adenovirus type 1 (MAV-1) infection; however, the molecular mechanism of this activity was not fully known. This work provides evidence about the MAV-1 protein that induces PKR degradation and expands knowledge about involvement of the proteasome pathway.The majority of the genes present in bacterial genomes remain poorly characterized, with up to one-third of those that are protein encoding having no definitive function. Transposon insertion sequencing represents a high-throughput technique that can help rectify this deficiency. The technology, however, can only be realistically applied to those species in which high rates of DNA transfer can be achieved. Here, we have developed a number of approaches that overcome this barrier in the autotrophic species Clostridium autoethanogenum by using a mariner-based transposon system. The inherent instability of such systems in the Escherichia coli conjugation donor due to transposition events was counteracted through the incorporation of a conditionally lethal codA marker on the plasmid backbone. Relatively low frequencies of transformation of the plasmid into C. autoethanogenum were circumvented through the use of a plasmid that is conditional for replication coupled with the routine implementation of an Illumina li of gene essentiality under heterotrophic and autotrophic growth, providing insights into the utilization of CO as a sole carbon and energy source. The strategies implemented are translatable and will allow others to apply transposon insertion sequencing to other microbes where DNA transfer has until now represented a barrier to progress.Healthy development and function of essentially all physiological systems and organs, including the brain, require exposure to the microbiota of our mothers and of the natural environment, especially in early life. We also know that some infections, if we survive them, modulate the immune system in relevant ways. If we study the evolution of the immune and metabolic systems, we can understand how these requirements developed and the nature of the organisms that we need to encounter. We can then begin to identify the mechanisms of the beneficial effects of these exposures. Against this evolutionary background, we can analyze the ways in which the modern urban lifestyle, particularly for individuals experiencing low socioeconomic status (SES), results in deficient or distorted microbial exposures and microbiomes. Thus, an evolutionary approach facilitates the identification of practical solutions to the growing scandal of health disparities linked to inequality.Aquatic fishes face osmotic stress continuously, and the gill is the first tissue that senses and responds to the external osmotic challenges. However, the understandings of how the gill microbiota could respond to osmotic stress and their potential host-bacterium relationships are limited. The objectives of the current study are to identify the hypotonic responsive genes in the gill cells and profile the gill microbiota communities after fresh water transfer experiment via transcriptome sequencing and 16S rRNA gene sequencing. Transcriptome sequencing identified 1,034 differentially expressed genes (DEGs), such as aquaporin and sodium potassium chloride cotransporter, after the fresh water transfer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further highlighted the steroid biosynthesis and glycosaminoglycan biosynthesis pathways in the gill. Moreover, the 16S rRNA gene sequencing identified Vibrio as the dominant bacterium in the seawater, which changed to Pseudomonas and Cetobacterium after the fresh water transfer. The alpha diversity analysis suggested that the gill bacterial diversity was lower in the fresh water transferred group. PIK-90 clinical trial The KEGG and MetaCyc analysis further predicted the alteration of the glycosaminoglycan and chitin metabolisms in the gill bacteria. Collectively, the common glycosaminoglycan and chitin pathways in both the gill cells and gill microbiota suggest the host-bacterium interaction in gill facilitates the fresh water acclimation. IMPORTANCE This is the first study using the transcriptome and 16S rRNA gene sequencing to report the hypotonic responsive genes in gill cells and the compositions of gill microbiota in marine medaka. The overlapped glycosaminoglycan- and chitin-related pathways suggest host-bacterium interaction in fish gill during osmotic stress.Purpose Chronic pain experienced by children and adolescents represents a significant burden in terms of health, quality of life, and economic costs to U.S. families. In 2015, the Boston Medical Center (BMC) Interdisciplinary Pain Clinic initiated an Integrative Medicine (IM) team model to address chronic pain in children. Team members included a pediatrician, child psychologist, physical therapist, acupuncturist, and massage therapist. Children were referred to the pain clinic from primary care and specialty services within BMC, the largest safety-net hospital in the northeastern United States. For this observational assessment, consent and assent were obtained from parents and pediatric patients. Individualized treatment plans were recommended by the IM team. Methods Self-reported survey and electronic medical record data were collected about socioeconomic demographics, pain, use of medical and IM services, and quality of life. The authors compared health and quality of life indicators and costs of care forn an interdisciplinary team approach is safe, feasible, and acceptable to families. Considerable cost savings were observed in the area of surgical procedures, hospitalizations, and consultations with specialists.Monoclonal antibody (mAb)-based immunotherapies targeting systemic and deep-seated fungal infections are still in their early stages of development, with no licensed antifungal mAbs currently being available for patients at risk. The cell wall glycoproteins of Candida albicans are of particular interest as potential targets for therapeutic antibody generation due to their extracellular location and key involvement in fungal pathogenesis. Here, we describe the generation of recombinant human antibodies specifically targeting two key cell wall proteins (CWPs) in C. albicans Utr2 and Pga31. These antibodies were isolated from a phage display antibody library using peptide antigens representing the surface-exposed regions of CWPs expressed at elevated levels during in vivo infection. Reformatted human-mouse chimeric mAbs preferentially recognized C. albicans hyphal forms compared to yeast cells, and increased binding was observed when the cells were grown in the presence of the antifungal agent caspofungin. In J774.1 macrophage interaction assays, mAb pretreatment resulted in the faster engulfment of C. albicans cells, suggesting a role of the CWP antibodies as opsonizing agents during phagocyte recruitment. Finally, in a series of clinically predictive mouse models of systemic candidiasis, our lead mAb achieved improved survival (83%) and a several-log reduction of the fungal burden in the kidneys, similar to the levels achieved for the fungicidal drug caspofungin and superior to the therapeutic efficacy of any anti-Candida mAb reported to date.Background Communication challenges in the neonatal intensive care unit include fragmented communication, challenges managing expectations amidst uncertainty, and navigating complex medical information. Social workers are well suited to mitigate these challenges. Objective In this study, we aimed to characterize the extent and nature of social worker participation in family conferences for critically ill infants. Design We used a longitudinal observational mixed-methods design, enrolling infants with a neurological condition, their parent(s), and their clinicians. All audio-recorded conferences were transcribed and de-identified. Emergent themes and subthemes were identified using conventional content analysis. Results We enrolled 40 infants and 61 parents. Sixty-eight conferences were held and audio recorded for 24 infants. Social workers were present for 51 of these conferences (n = 51/68, 75%) across 18 cases (n = 18/24, 75%). We identified four themes, conceptualized as distinct roles played by social workers in family conferences (1) Translator social workers served as a communicative bridge between parents and the medical team; (2) Coordinator social workers simplified logistics and connected parents to community resources, including home health agencies and financial assistance; (3) Expectation manager social workers provided anticipatory guidance and helped parents conceptualize the remainder of the hospital stay, discharge, and life at home; and (4) Advocate social workers validated parental values and concerns and provided immediate emotional support. Conclusions Social workers participated in three-quarters of family conferences for critically ill infants. When they participated, they facilitated communication, coordinated care, managed expectations, and advocated for families. These findings underscore the important, varied, and concurrent roles social workers play in the care of critically ill infants. Future communication and family support interventions should leverage these distinct roles.Objective To determine the effects of augmented reality (AR) interventions on the upper extremity's (UE's) range of motion (ROM) and muscle strength in children with spastic hemiplegic cerebral palsy (SHCP). Materials and Methods Thirty children with SHCP, aged 6 to 12 years, were randomly divided into three interventional groups. Each group received an AR game that is, Balance It, Bubble Pop, or Scoop'd (WonderTree, Pakistan). The UE's ROM and muscle strength were assessed at the baseline and after 8 weeks of intervention through goniometer and manual muscle testing, respectively. Paired-sample t-test and Wilcoxon signed-rank test were used for analyzing the changes in ROM and muscle strength within the groups respectively. One-way analysis of variance (ANOVA) and Tukey's test were used for the differences in ROM, whereas the Kruskal-Wallis test was used for the differences in muscle strength, between the groups. Results Within-group analysis revealed that all the groups significantly improved in ROM of the majority of joints and in the strength of various muscles of UE (P 0.05). Conclusion The AR games intervention was beneficial and effective for improving the ROM of majority of the joints and strength of various muscles of UE in children with SHCP. Clinical Trial Registration number NCT04171232.Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de novo synthase (FAS), they depend on host-derived fatty acids. AMF colonization is accompanied by expression of specific lipid genes and synthesis of sn-2 monoacylglycerols (MAGs). It is unknown how host-derived fatty acids are taken up by AMF. We describe the characterization of two AMP-binding domain protein genes from Rhizophagus irregularis, RiFAT1 and RiFAT2, with sequence similarity to Saccharomyces cerevisiae fatty acid transporter 1 (FAT1). Uptake of 13C-myristic acid (140) and, to a lesser extent, 13C-palmitic acid (160) was enhanced after expression of RiFAT1 or RiFAT2 in S. cerevisiae Δfat1 cells. The uptake of 2H-labeled fatty acids from 2H-myristoylglycerol or 2H-palmitoylglycerol was also increased after RiFAT1 and RiFAT2 expression in Δfat, but intact 2H-MAGs were not detected. RiFAT1 and RiFAT2 expression was induced in colonized roots compared with extraradical mycelium.