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Stem cell transplantation therapies are currently under investigation for central nervous system disorders. Although preclinical models show benefit, clinical translation is somewhat limited by the absence of reliable noninvasive methods to confirm targeting and monitor transplanted cells in vivo. Here, we assess a novel magnetic resonance imaging (MRI) contrast agent derived from magnetotactic bacteria, magneto-endosymbionts (MEs), as a translatable methodology for in vivo tracking of stem cells after intracranial transplantation. We show that ME labeling provides robust MRI contrast without impairment of cell viability or other important therapeutic features. Labeled cells were visualized immediately post-transplantation and over time by serial MRI in nonhuman primate and mouse brain. Postmortem tissue analysis confirmed on-target grft location, and linear correlations were observed between MRI signal, cell engraftment, and tissue ME levels, suggesting that MEs may be useful for determining graft survival or rejection. Overall, these findings indicate that MEs are an effective tool for in vivo tracking and monitoring of cell transplantation therapies with potential relevance to many cellular therapy applications.
As a member of natural resistance-associated macrophage protein (Nramp) family, Nramp2 conservatively exists in the cell membrane across species and is essential for normal iron homeostasis in an H+-dependent manner. Withholding available iron represents an important host defense strategy. However, the function of Nramp2 in response to invading pathogens is largely unknown in invertebrates. In this study, a unique echinoderm Nramp2 was identified from sea cucumber Apostichopus japonicus (designated as AjNramp2). The cDNA sequence of AjNramp2 was 2360 bp, with a putative open reading frame of 1713 bp, encoding a typical Nramp domain containing protein with 570 amino acid residues. Structural analysis revealed that AjNramp2 consisted of highly conserved helix regions similar with the human Nramp2. Spatial expression analysis revealed that AjNramp2 was ubiquitously expressed in all examined tissues, with the highest level found in the intestine. Immunohistochemistry assay showed that AjNramp2 was mainly located in the cellular membrane in coelomocytes. Vibrio splendidus challenge and lipopolysaccharide (LPS) stimulation could significantly promote the expression of AjNramp2, which was consistent with the cellular iron level in coelomocytes. Moreover, when the expression of AjNramp2 was knocked down by siRNA-AjNramp2, the cellular iron level was coordinately decreased in coelomocytes under LPS stimulation. Taken together, results indicated that AjNramp2 serves as an iron transport receptor to withhold available iron and may contribute to the nutritional immunity defense system of sea cucumber.
Toll-like receptors (TLRs) are major pattern recognition receptors (PRRs) that recognize multiple pathogen-associated molecular patterns (PAMPs) through the leucine-rich repeat (LRR) domain and mount effective immune responses. Vibrio parahaemolyticus is the main pathogen that causes vibriosis in aquatic animals, yet the mechanisms of its recognition by innate immune system in teleost fish remain unknown. Here, the results reveal that TLR13 in orange-spotted grouper (Epinephelus coioides) (EcTLR13) recognizes a conserved 23S ribosomal RNA (23S rRNA) sequence in V. parahaemolyticus, and the 13-nucleotide motif near the 23S rRNA ribozyme activation site (VP13) acts as a PAMP. After challenge with RNA and 23S rRNA from V. parahaemolyticus and with the synthetic oligoribonucleotide VP13, the expression of EcTLR13 in grouper spleen cells (GS cells) was significantly increased. EcTLR13-knockdowned GS cells were stimulated with the same stimulants as listed above, the expression of IL-6, IL-12, IL-1β and TNFα was significantly reduced. RNA-protein immunoprecipitation revealed that VP13 could directly bind to EcTLR13. The dual-luciferase reporter assay also showed that EcTLR13 enhanced the fluorescence activity of IFNβ rather than that of NF-κB when the cells were challenged with RNA from V. parahaemolyticus or with synthetic VP13. Our study established the mechanism of fish TLR13-mediated recognition of microbial products during V. parahaemolyticus infection.
More than 40 human diseases, mainly diseases affecting the central nervous system, are caused by the expansion of unstable nucleotide repeats. Repeats of sequences like (CAG)n present in different genes can be responsible for various diseases of the central nervous system. An expanded hexanucleotide repeat (GGGGCC)n in the C9ORF72 gene has been characterized as the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar dementia. In this study, we performed a genome-wide analysis in the human genome and identified 74 genes containing this precise hexanucleotide repeat, with a preference for a location in exon 1 or intron 1, similar to the C9ORF72 gene. A total of 36 of these 74 genes may be of interest as candidates in neurodevelopmental or neurodegenerative diseases, based on their function.
The developmental trajectory of the primate brain varies substantially with aging across subjects. However, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. Based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3D template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thickness (CT) and regional gray matter volume (GMV). We observed an overall decrease in total GMV and mean CT, and an increase in white matter volume from juvenile to early adult. Specifically, CT and regional GMV were greater in prefrontal and temporal cortices relative to early unimodal areas. Age-dependent trajectories of thickness and volume for each cortical region revealed an increase in the medial temporal lobe, and decreases in all other regions. A low percentage of highly individualized deviations of CT and GMV were identified (0.0021%, 0.0043%, respectively, P < 0.05, false discovery rate [FDR]-corrected). Our approach provides a natural framework to parse individual neuroanatomical differences for use as a reference standard in macaque brain research, potentially enabling inferences regarding the degree to which behavioral or symptomatic variables map onto brain structure in future disease studies.
Childhood sexual abuse (CSA) has been shown to be more prevalent among populations living with HIV. Antiretroviral therapy (ART) adherence is crucial for populations living with HIV as it significantly increases the likelihood of attaining and maintaining viral suppression. Previous findings on the association between CSA and ART adherence have been mixed. The current mixed-methods systematic review aimed to identify quantitative and qualitative studies from CINAHL, PsycInfo, PubMed, and Web of Science examining the relationship between CSA and ART adherence. Authors were also contacted if relevant data were unpublished. Studies had to be published from January 1, 2000 to April 1, 2019, written in English, and examined CSA as an exposure and ART adherence as an outcome. Four domains were combined: (1) childhood sexual abuse; (2) child; (3) antiretroviral; and (4) adherence. Eight quantitative and two qualitative studies were retained. The results showed that four quantitative studies found no association while the other four found factors such as timing of victimization, mental health and gender influenced the association between CSA and ART adherence. Themes emerging from the qualitative studies included use of ART evoking memories of CSA; CSA impacting mental health; and mental health treatment improving ART adherence. Mixed insights included the intricate links between CSA and ART adherence and the role of external factors on the relationship. ART adherence intervention programs may be needed for people who have experienced CSA. However, future studies are needed that will examine the association between CSA and ART adherence and include subgroup analyses.
The objective of this study was to evaluate the ex vivo effect of cyclic loading on the stability of screws placed in locking plates used to bridge segmental bone defects. The primary interface stability was assessed using peak reverse torque. Eighteen, 8-hole stainless-steel 4.5 mm locking plates and 4.0-mm self-tapping locking-head screws were used to stabilize 40-mm segmental defects in goat tibiae. Treatment groups included control constructs without cyclic loading (n = 6) and constructs tested to 5000 (n = 6) and 10,000 cycles (n = 6) of 600 N compressive axial loading. The insertion of all screws was standardized to 400 N-cm insertion torque. Peak reverse torque was measured immediately after screw placement (control), or after the completion of the respective loading cycles. The difference between treatment groups was compared using univariate analysis of variance. The analysis revealed a significant difference in peak reverse torque of the screws among the treatment groups (p = .000). The mean reverse torque values equaled 343.5 ± 18.3 N-cm for non-cycled controls, 303.3 ± 25.9 and 296.0 ± 42.9 N-cm after 5000 and 10,000 cycles, respectively. Among all treatment groups, screws placed in the distal bone segment tended to have lesser peak reverse torque reduction than those placed in the proximal segment and the difference was proportional to the number of cycles (p = .562; p = .255; p = .013 in control, and after 5000 and 10,000 cycles, respectively). Cyclic loading may have a negative effect on the primary stability of screws placed in locking plate constructs used to bridge segmental bone defects and could contribute to the risk of screw loosening.
Urinary tract infection is the most common complication after urodynamic studies (UDS). Practice guidelines recommend against antibiotic prophylaxis based on an outdated review of the literature, which advised on the premise of "a lack of good quality studies" and based on an assumed low incidence not consistently supported by the literature.
The gastrojejunostomy during laparoscopic Roux-en-Y gastric bypass (LRYGB) can be constructed by hand sewn (HSA), linear (LSA) and circular (CSA) stapler technique. They are all considered safe; however, it is not known which the best technique is. Short-term follow-up suggest no difference in weight loss or weight regain between them. However, there is no information on these parameters in the long term. Theatre time and cost are other important factors defining the best way to form gastrojejunostomy.
The outbreak of SARS-CoV-2 has made us all think critically about hospital indoor air quality and the approaches to remove, dilute, and disinfect pathogenic organisms from the hospital environment. While specific aspects of the coronavirus infectivity, spread, and routes of transmission are still under rigorous investigation, it seems that a recollection of knowledge from the literature can provide useful lessons to cope with this new situation. As a result, a systematic literature review was conducted on the safety of air filtration and air recirculation in healthcare premises. This review targeted a wide range of evidence from codes and regulations, to peer-reviewed publications, and best practice standards. The literature search resulted in 394 publications, of which 109 documents were included in the final review. Overall, even though solid evidence to support current practice is very scarce, proper filtration remains one important approach to maintain the cleanliness of indoor air in hospitals. Given the rather large physical footprint of the filtration system, a range of short-term and long-term solutions from the literature are collected. Nonetheless, there is a need for a rigorous and feasible line of research in the area of air filtration and recirculation in healthcare facilities. Such efforts can enhance the performance of healthcare facilities under normal conditions or during a pandemic. Past innovations can be adopted for the new outbreak at low-to-minimal cost.
The signal transducer and activator of transcription (STAT), as an important transcription factor of the Janus kinase (JAK)-STAT signaling pathway, is pivotal for development and immunity and well documented in vertebrates. However, the STAT gene has not been reported in chordate amphioxus (Branchiostoma belcheri). In this study, we firstly identify and characterize two STAT genes from Branchiostoma belcheri (designed as AmphiSTATa and AmphiSTATb). Secondly, our results reveal that AmphiSTATa is clustered with vertebrate STAT1, STAT2, STAT3 and STAT4, whereas AmphiSTATb is grouped with STAT5 and STAT6 based on phylogenetic analysis. Thirdly, AmphiSTATa and AmphiSTATb are found to widely express in five representative tissues of amphioxus (gill, hepatic cecum, intestine, muscle and notochord) by RT-qPCR analysis. Importantly, both AmphiSTATa and AmphiSTATb can be involved in innate immune responses to LPS stimulation. Fourthly, we demonstrate that AmphiSTATa and AmphiSTATb can form homodimers or heterodimers by Co-IP and Native-PAGE assay, and that AmphiSTATa and AmphiSTATb proteins can also distribute in cytoplasm and nucleus by the subcellular localization. Taken together, our findings not only reveal the roles of AmphiSTATa and AmphiSTATb in amphioxus innate immune responses to LPS stimulation, but provide a new insight into further elucidating the evolution and function of STATs in animals.
The classification of viruses is relevant to a number of scientific and clinical disciplines, including the practice of diagnostic virology. Here, we provide an update to our previous review of taxonomic changes for disease-causing viruses in humans and vertebrate animals, covering changes between 2018 and 2020. Recent advances in virus taxonomy structure by the International Committee on Taxonomy of Viruses inform this update.
Soilless culture systems offer an environmentally friendly and resource-efficient alternative to traditional cultivation systems fitting within the scheme of a circular economy. The objective of this research was to examine the sustainable integration of recycling fertilizers in hydroponic cultivation-creating a nutrient cycling concept for horticultural cultivation. Using the nutrient film technique (NFT), three recycling-based fertilizer variants were tested against standard synthetic mineral fertilization as the control, with 11 tomato plants (Solanum lycopersicum L. cv. Pannovy) per replicate (n = 4) and treatment: two nitrified urine-based fertilizers differing in ammonium/nitrate ratio (NH4+:NO3-), namely (1) "Aurin" (AUR) and (2) "Crop" (CRO); as well as (3) an organo-mineral mixture of struvite and vinasse (S+V); and (4) a control (NPK). The closed chamber method was adapted for gas fluxes (N2O, CH4, and CO2) from the root zone. There was no indication in differences of the total shoot biomass fresh matter and uptake of N, P and K between recycling fertilizers and the control. Marketable fruit yield was comparable between NPK, CRO and S+V, whereas lower yields occurred in AUR. The higher NH4+:NO3- of AUR was associated with an increased susceptibility of blossom-end-rot, likely due to reduced uptake and translocation of Ca. Highest sugar concentration was found in S+V, which may have been influenced by the presence of organic acids in vinasse. N2O emissions were highest in S+V, which corresponded to our hypothesis that N2O emissions positively correlate with organic-C input by the fertilizer amendments. Remaining treatments showed barely detectable GHG emissions. A nitrified urine with a low NH4+:NO3- (e.g., CRO) has a high potential as recycling fertilizer in NFT systems for tomato cultivation, and S+V proved to supply sufficient P and K for adequate growth and yield. Alternative cultivation strategies may complement the composition of AUR.
Cardiac diastolic dysfunction in aging arises from increased ventricular stiffness caused by inflammation and interstitial fibrosis. The diastolic dysfunction contributes to heart failure with preserved ejection fraction (HFpEF), which in the aging population is more common in women. This report examines its progression over 12 weeks in aging C57BL/6J mice and correlates its development with changes in macrophage polarization and collagen deposition.Aged C57BL/6J mice were injected with dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) ligand 1 (DCSL1, an anti-inflammatory agent) or saline for 12 weeks. Echo and Doppler measurements were performed before and after 4 and 12 weeks of treatment. DCSL1 prevented the worsening of diastolic dysfunction over time in females but not in males. Cardiac single cell suspensions analyzed by flow cytometry revealed changes in the inflammatory infiltrate: (1) in males, there was an increased total number of leukocytes with an increased pro-inflammatory profile compared with females and they did not respond to DCSL1; (2) by contrast, DCSL1 treatment resulted in a shift in macrophage polarization to an anti-inflammatory phenotype in females. Notably, DCSL1 preferentially targeted tumor necrosis factor-α (TNFα+) pro-inflammatory macrophages. The reduction in pro-inflammatory macrophage polarization was accompanied by a decrease in collagen content in the heart.Age-associated diastolic dysfunction in mice is more severe in females and is associated with unique changes in macrophage polarization in cardiac tissue. Treatment with DCSL1 mitigates the changes in inflammation, cardiac function, and fibrosis. The characteristics of diastolic dysfunction in aging female mice mimic similar changes in aging women.
Antenatal Doppler measurements of the fetal umbilical and cerebral circulations can predict perinatal complications; however, it is unclear if subtle variations in antenatal Doppler measurements are associated with long-term neurodevelopmental outcome. In this study, we examined whether antenatal Doppler measurements of the fetal-placental circulation are associated with cognitive and motor abilities and brain morphology in childhood.
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