ABSTRACT
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails.
Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Ebola Vaccines/immunology , Hemorrhagic Fever, Ebola/immunology , Amino Acid Sequence , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Complementarity Determining Regions , Cross Reactions , Ebolavirus/immunology , Epitope Mapping , Epitopes, B-Lymphocyte/immunology , Female , Ferrets , Guinea Pigs , Immunoglobulin Fab Fragments/ultrastructure , Macaca fascicularis , Male , Mice , Mice, Inbred BALB C , Models, MolecularABSTRACT
MITF, a basic Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. We perform a genetic screen for suppressors of the Mitf-associated pigmentation phenotype in mice and identify an intragenic Mitf mutation that terminates MITF at the K316 SUMOylation site, leading to loss of the C-end intrinsically disordered region (IDR). The resulting protein is more nuclear but less stable than wild-type MITF and retains DNA-binding ability. As a dimer, it can translocate wild-type and mutant MITF partners into the nucleus, improving its own stability thus ensuring nuclear MITF supply. smFRET analysis shows interactions between K316 SUMOylation and S409 phosphorylation sites across monomers; these interactions largely explain the observed effects. The recurrent melanoma-associated E318K mutation in MITF, which affects K316 SUMOylation, also alters protein regulation in concert with S409. This suggests that residues K316 and S409 of MITF are impacted by SUMOylation and phosphorylation, respectively, mediating effects on nuclear localization and stability through conformational changes. Our work provides a novel mechanism of genetic suppression, and an example of how apparently deleterious mutations lead to normal phenotypes.
ABSTRACT
One of the biggest environmental alterations we have made to our species is the change in the exposure to light. During the day, we typically sit behind glass windows illuminated by artificial light that is >400 times dimmer and has a very different spectrum than natural daylight. On the opposite end are the nights that are now lit up by several orders of magnitude. This review aims to provide food for thought as to why this matters for humans and other animals. Evidence from behavioral neuroscience, physiology, chronobiology, and molecular biology is increasingly converging on the conclusions that the biological nonvisual functions of light and photosensory molecules are highly complex. The initial work of von Frisch on extraocular photoreceptors in fish, the identification of rhodopsins as the molecular light receptors in animal eyes and eye-like structures and cryptochromes as light sensors in nonmammalian chronobiology, still allowed for the impression that light reception would be a relatively restricted, localized sense in most animals. However, light-sensitive processes and/or sensory proteins have now been localized to many different cell types and tissues. It might be necessary to consider nonlight-responding cells as the exception, rather than the rule.
Subject(s)
Cryptochromes , Photoreceptor Cells, Invertebrate , Humans , Animals , Photoreceptor Cells, Invertebrate/physiologyABSTRACT
Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43 mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15 mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51 µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.
Subject(s)
Antineoplastic Agents , Cordyceps , Neoplasms , Penicillium , Humans , Penicillium/genetics , Fruiting Bodies, FungalABSTRACT
The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.
Subject(s)
Chromosomes, Human, Pair 10 , Disease Resistance/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Mycobacterium tuberculosis , Quantitative Trait Loci , Tuberculosis/genetics , Tuberculosis/microbiology , Alleles , Computational Biology/methods , France , Genotype , Humans , Meta-Analysis as Topic , Population Groups/genetics , South Africa , VietnamABSTRACT
Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.
Subject(s)
Anti-Bacterial Agents , Colistin , Drug Resistance, Bacterial , Humans , Colistin/pharmacology , Colistin/therapeutic use , Vietnam/epidemiology , Male , Female , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Prevalence , Middle Aged , Feces/microbiology , Aged , Microbial Sensitivity TestsABSTRACT
Marburg virus (MARV) causes a hemorrhagic fever disease in human and nonhuman primates with high levels of morbidity and mortality. Concerns about weaponization of aerosolized MARV have spurred the development of nonhuman primate (NHP) models of aerosol exposure. To address the potential threat of aerosol exposure, a monoclonal antibody that binds MARV glycoprotein was tested, MR186YTE, for its efficacy as a prophylactic. MR186YTE was administered intramuscularly to NHPs at 15 or 5 mg/kg 1 month prior to MARV aerosol challenge. Seventy-five percent (3/4) of the 15 mg/kg dose group and 50% (2/4) of the 5 mg/kg dose group survived. Serum analyses showed that the NHP dosed with 15 mg/kg that succumbed to infection developed an antidrug antibody response and therefore had no detectable MR186YTE at the time of challenge. These results suggest that intramuscular dosing of mAbs may be a clinically useful prophylaxis for MARV aerosol exposure.
Subject(s)
Marburg Virus Disease , Marburgvirus , Animals , Humans , Antibodies, Monoclonal , Primates , AerosolsABSTRACT
This experimental study investigates the effects of several heuristic cues and systematic factors on users' misinformation susceptibility in the context of health news. Specifically, it examines whether author credentials, writing style, and verification check flagging influence participants' intent to follow article behavioral recommendations provided by the article, perceived article credibility, and sharing intent. Findings suggest that users rely only on verification checks (passing/failing) in assessing information credibility. Of the two antecedents to systematic processing, social media self-efficacy moderates the links between verification and participants' susceptibility. Theoretical and practical implications are discussed.
ABSTRACT
Background: Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. Materials and methods: A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Results: Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. Conclusions: VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.
ABSTRACT
Leprosy is a chronic disease caused by Mycobacterium leprae. Worldwide, more than 200,000 new patients are affected by leprosy annually, making it the second most common mycobacterial disease after tuberculosis. The MHC/HLA region has been consistently identified as carrying major leprosy susceptibility variants in different populations at times with inconsistent results. To establish the unambiguous molecular identity of classical HLA class I and class II leprosy susceptibility factors, we applied next-generation sequencing to genotype with high-resolution 11 HLA class I and class II genes in 1,155 individuals from a Vietnamese leprosy case-control sample. HLA alleles belonging to an extended haplotype from HLA-A to HLA-DPB1 were associated with risk to leprosy. This susceptibility signal could be reduced to the HLA-DRB1*10:01~ HLA-DQA1*01:05 alleles which were in complete linkage disequilibrium (LD). In addition, haplotypes containing HLA-DRB3~ HLA-DRB1*12:02 and HLA-C*07:06~ HLA-B*44:03~ HLA-DRB1*07:01 alleles were found as two independent protective factors for leprosy. Moreover, we replicated the previously associated HLA-DRB1*15:01 as leprosy risk factor and HLA-DRB1*04:05~HLA-DQA1*03:03 as protective alleles. When we narrowed the analysis to the single amino acid level, we found that the associations of the HLA alleles were largely captured by four independent amino acids at HLA-DRß1 positions 57 (D) and 13 (F), HLA-B position 63 (E) and HLA-A position 19 (K). Hence, analyses at the amino acid level circumvented the ambiguity caused by strong LD of leprosy susceptibility HLA alleles and identified four distinct leprosy susceptibility factors.
Subject(s)
Amino Acids/genetics , Genetic Predisposition to Disease , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class I/genetics , Leprosy/pathology , Mutation , Adolescent , Adult , Female , Haplotypes , Humans , Leprosy/genetics , Male , Young AdultABSTRACT
Leprosy is a chronic infectious disease of the skin and peripheral nerves with a strong genetic predisposition. Recent genome-wide approaches have identified numerous common variants associated with leprosy, almost all in the Chinese population. We conducted the first family-based genome-wide association study of leprosy in 622 affected offspring from Vietnam, followed by replication in an independent sample of 1181 leprosy cases and 668 controls of the same ethnic origin. The most significant results were observed within the HLA region, in which six SNPs displayed genome-wide significant associations, all of which were replicated in the independent case/control sample. We investigated the signal in the HLA region in more detail, by conducting a multivariate analysis on the case/control sample of 319 GWAS-suggestive HLA hits for which evidence for replication was obtained. We identified three independently associated SNPs, two located in the HLA class I region (rs1265048: OR = 0.69 [0.58-0.80], combined p-value = 5.53x10-11; and rs114598080: OR = 1.47 [1.46-1.48], combined p-value = 8.77x10-13), and one located in the HLA class II region (rs3187964 (OR = 1.67 [1.55-1.80], combined p-value = 8.35x10-16). We also validated two previously identified risk factors for leprosy: the missense variant rs3764147 in the LACC1 gene (OR = 1.52 [1.41-1.63], combined p-value = 5.06x10-14), and the intergenic variant rs6871626 located close to the IL12B gene (OR = 0.73 [0.61-0.84], combined p-value = 6.44x10-8). These results shed new light on the genetic control of leprosy, by dissecting the influence of HLA SNPs, and validating the independent role of two additional variants in a large Vietnamese sample.
Subject(s)
Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class I/genetics , Leprosy/genetics , Polymorphism, Single Nucleotide , Female , Genome-Wide Association Study , Humans , Interleukin-12 Subunit p40/genetics , Intracellular Signaling Peptides and Proteins/genetics , Leprosy/epidemiology , MaleABSTRACT
Type-1 reactions (T1R) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the genewise enrichment of rare protein-altering variants in 7 genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy patients of which 237 were T1R-affected and 237 were T1R-free matched controls. Genewise enrichment of nonsynonymous variants was tested with both kernel-based (sequence kernel association test [SKAT]) and burden methods. Of the 7 genes tested 2 showed statistical evidence of association with T1R. For the LRRK2 gene an enrichment of nonsynonymous variants was observed in T1R-free controls (PSKAT-O = 1.6 × 10-4). This genewise association was driven almost entirely by the gain-of-function variant R1628P (P = 0.004; odds ratio = 0.29). The second genewise association was found for the Parkin coding gene PRKN (formerly PARK2) where 7 rare variants were enriched in T1R-affected cases (PSKAT-O = 7.4 × 10-5). Mutations in both PRKN and LRRK2 are known causes of Parkinson's disease (PD). Hence, we evaluated to what extent such rare amino acid changes observed in T1R are shared with PD. We observed that amino acids in Parkin targeted by nonsynonymous T1R-risk mutations were also enriched for mutations implicated in PD (P = 1.5 × 10-4). Hence, neuroinflammation in PD and peripheral nerve damage due to inflammation in T1R share overlapping genetic control of pathogenicity.
Subject(s)
Leprosy , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 , Mutation , Parkinson Disease , Ubiquitin-Protein Ligases , Female , Humans , Leprosy/genetics , Leprosy/metabolism , Leprosy/pathology , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Male , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
BACKGROUND: Treatment for large defects in the non-weight-bearing Achilles tendon and soft tissues remains a reconstructive challenge. The free composite anterolateral thigh flap (ALT) with fascia lata (FL) has been indicated in the single-stage reconstruction of the Achilles tendon and soft tissue defect and this technique remain some disadvantages, such as the inability to perform primary flap thinning, requiring secondary flap thinning, and the delayed normalization of the range of motion of the ankle joint. The free chimeric ALT flap with FL was introduced as a novel alternative with many advantages in reconstructing the Achilles tendon and soft tissue defects. This paper reports the reconstruction of the massive Achilles tendon and overlying skin defects using free chimeric ALT flaps with FL. METHODS: From June 2017 to October 2020, we performed on a series of 5 patients receiving free chimeric ALT flaps with FL to reconstruct the Achilles tendon and soft tissue defects. The age of patients ranged from 43 to 62 years old. All five patients had full-layer defects of the Achilles tendon with infection. The sizes of the skin defects ranged from 6 × 4 cm to 12 × 10 cm. The perforators from the descending branch of the lateral circumflex femoral arteries are located using a handheld Doppler. The perforators help to design the outline of the ALT flap and fascia flap. The skin flap was thinned under microscopy if the flap was too thick. The anastomosis was accomplished before insetting the flaps into the defect. RESULTS: The size of the ALT flap ranged from 10 × 5 cm to 15 × 12 cm, and the size of the FL flap ranged from 7 × 4 cm to 10 × 8 cm. The mean perforator length for the skin flap and fascia lata was 3.3 cm (range, 2.5-5.0 cm) and 5.3 cm (range, 3.5-7.0 cm), respectively. Four patients received skin flap thinning up to 57%-79% of the flap thickness, while one patient did not need to debulk. The thickness of the ALT flap ranged from 6 to 13 mm. All the flaps survived completely and postoperative courses were uneventful without any complications. The follow-up time ranged from 12 to 51 months. All patients were able to stand and ambulate, and they were satisfied with the reconstructive results. CONCLUSIONS: The free thin chimeric ALT with FL flap is appeared to be an appropriate treatment for the massive Achilles tendon and overlying skin defects. This may be a practical approach to improve the functional outcomes of patients with infected massive Achilles tendon and overlying skin defects.
Subject(s)
Achilles Tendon , Free Tissue Flaps , Perforator Flap , Plastic Surgery Procedures , Soft Tissue Injuries , Achilles Tendon/surgery , Adult , Fascia Lata/transplantation , Free Tissue Flaps/surgery , Humans , Middle Aged , Perforator Flap/surgery , Plastic Surgery Procedures/methods , Skin Transplantation/methods , Soft Tissue Injuries/surgery , Thigh/surgeryABSTRACT
Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which is caused by the lack or the drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore the expression of dystrophin. While significant progress was achieved, the therapeutic benefit of treated patients is still unsatisfactory. Efficiency in gene therapy for DMD is hampered not only by incompletely resolved technical issues, but likely also due to the progressive nature of DMD. It is indeed suspected that some of the secondary pathologies, which are evolving over time in DMD patients, are not fully corrected by the restoration of dystrophin expression. We recently identified perturbations of the mevalonate pathway and of cholesterol metabolism in DMD patients. Taking advantage of the mdx model for DMD, we then demonstrated that some of these perturbations are improved by treatment with the cholesterol-lowering drug, simvastatin. In the present investigation, we tested whether the combination of the restoration of dystrophin expression with simvastatin treatment could have an additive beneficial effect in the mdx model. We confirmed the positive effects of microdystrophin, and of simvastatin, when administrated separately, but detected no additive effect by their combination. Thus, the present study does not support an additive beneficial effect by combining dystrophin restoration with a metabolic normalization by simvastatin.
Subject(s)
Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/therapy , Simvastatin/administration & dosage , Animals , Disease Models, Animal , Genetic Therapy/methods , Male , Mice , Mice, Inbred mdx , Muscle, Skeletal/drug effectsABSTRACT
Glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate pathway. The reaction catalyzed by the enzyme is considered to be the main source of reducing power for nicotinamide adenine dinucleotide phosphate (NADPH) and is a precursor of 5-carbon sugar used by cells. To uncover the structural features of the enzyme, we determined the crystal structures of glucose-6-phosphate dehydrogenase from Kluyveromyces lactis (KlG6PD) in both the apo form and a binary complex with its substrate glucose-6-phosphate. KlG6PD contains a Rossman-like domain for cofactor NADPH binding; it also presents a typical antiparallel ß sheet at the C-terminal domain with relatively the same pattern as those of other homologous structures. Moreover, our structural and biochemical analyses revealed that Lys153 contributes significantly to substrate G6P recognition. This study may provide insights into the structural variation and catalytic features of the G6PD enzyme.
Subject(s)
Glucosephosphate Dehydrogenase/chemistry , Glucosephosphate Dehydrogenase/metabolism , Kluyveromyces/enzymology , Amino Acid Sequence , Apoenzymes/chemistry , Apoenzymes/genetics , Apoenzymes/metabolism , Binding Sites , Catalytic Domain , Crystallography, X-Ray , Glucosephosphate Dehydrogenase/genetics , Kinetics , Models, Molecular , Mutagenesis , Structure-Activity Relationship , Substrate SpecificityABSTRACT
Melanocytes originate in the neural crest as precursor cells which then migrate and proliferate to reach their destination where they differentiate into pigment-producing cells. Melanocytes not only determine the colour of hair, skin and eyes but also protect against the harmful effects of UV irradiation. The establishment of the melanocyte lineage is regulated by a defined set of transcription factors and signalling pathways that direct the specific gene expression programmes underpinning melanoblast specification, survival, migration, proliferation and differentiation. In addition, epigenetic modifiers and replacement histones play key roles in regulating gene expression and its timing during the different steps of this process. Here, we discuss the evidence for the role of epigenetic regulators in melanocyte development and function and how they interact with transcription factors and signalling pathways to establish and maintain this important cell lineage.
Subject(s)
Epigenesis, Genetic , Homeostasis/genetics , Melanocytes/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Cell Lineage , Humans , MiceABSTRACT
Guided by the health risk communication literature and the social identity model of deindividualization effects, this study examines whether and how concurrent exposure to health news articles and congruent/incongruent comments posted by anonymous others may affect news viewers' personal risk perception, societal risk perception, and intention to communicate about health risk issues. Two controlled experiments were conducted in Vietnam concerning two controversial health risk issues, including ear picking and child corporal punishment. Results showed a significant interaction effect between comments and perceived similarity on personal risk perception and societal risk perception, such that comments influenced both types of risk perception when viewers perceived that anonymous commenters were ingroup members. Results also indicated the joint effect of comments and perceived similarity on participants' intention to communicate, mediated by their personal risk perception and societal risk perception. Theoretical and practical implications were discussed.
Subject(s)
Health Communication , Intention , Child , Humans , PerceptionABSTRACT
Phosphorus (P) concentration beyond threshold limit can trigger eutrophication in stagnant water bodies nevertheless it is an indispensable macronutrient for aquatic life. Even in low P concentration (≤1 mg L-1), P can be detrimental for ecosystem's health, but this aspect has not been thoroughly investigated. The elimination of low P content is rather expensive or complex. Therefore, a unique and sustainable approach has been proposed in which valorized bivalve seashells can be used for the removal of low P content. Initially, acicular shaped aragonite particles (~21 µm) with an aspect ratio of around 21 have been synthesized through the wet carbonation process and used to treat aqueous solutions containing P in low concentration (P ≤ 1 mg L-1). Response surface methodology based Box-Behnken design has been employed for optimization study which revealed that with aragonite dosage (140 mg), equilibrium pH (~10.15), and temperature (45 °C), a phosphorus removal efficiency of ~97% can be obtained in 10 h. The kinetics and isotherm studies have also been carried out (within the range P ≤ 1 mg L-1) to investigate a probable removal mechanism. Also, aragonite demonstrates higher selectivity (>70%) towards phosphate with coexisting anions such as nitrate, chloride, sulfate, and carbonate. Through experimental data, elemental mapping, and molecular dynamic simulation, it has been observed that the removal mechanism involved a combination of electrostatic adsorption of Ca2+ ions on aragonite surface and chemical interaction between the calcium and phosphate ions. The present work demonstrates a sustainable and propitious potential of seashell derived aragonite for the removal of low P content in aqueous solution along with its unconventional mechanistic approach.
Subject(s)
Calcium Carbonate , Water Pollutants, Chemical , Adsorption , Animal Shells , Animals , Ecosystem , Hydrogen-Ion Concentration , Kinetics , Phosphates , Phosphorus , WaterABSTRACT
Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of current standard of care. A near-infrared pH-sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N-isopropyl Acrylamide) nanoparticles conjugated with pH-sensitive (CypHer5E) and pH-insensitive (Cy7) fluorescent dyes into 2-hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH-sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on wound contact side of discarded wound gauze, the pH and its non-homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near-infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real time.
Subject(s)
Exudates and Transudates/chemistry , Wound Healing/physiology , Acrylamides/chemistry , Bandages , Fluorescent Dyes , Humans , Hydrogels , Hydrogen-Ion Concentration , Methacrylates , Nanoparticles , Skin/injuries , Skin Diseases/physiopathology , Wounds and Injuries/physiopathologyABSTRACT
We have systematically investigated the magnetization reversal characteristics and magnetoresistance of continuous and nanoporous [Co/Pd]5-IrMn multilayered thin films with perpendicular magnetic anisotropy at different temperatures (4-300 K). For their nanostructuring, porosity was induced by means of deposition onto templates of anodized titania with small (â¼30 nm in diameter) homogeneously distributed pores. The magnetization reversal and magnetoresistance of the porous films were found to be closely related to the splitting of the ferromagnetic material into regions with different magnetic properties, in correlation with the complex morphology of the porous system. Independent magnetization reversal is detected for these regions, and is accompanied by its strong impact on the magnetic order in the capping IrMn layer. Electron-magnon scattering is found to be a dominant mechanism of magnetoresistance, determining its almost linear field dependence in a high magnetic field and contributing to its magnetoresistance behavior, similar to magnetization reversal, in a low magnetic field. Partial rotation of IrMn magnetic moments, consistent with the magnetization reversal of the ferromagnet, is proposed as an explanation for the two-state resistance behavior observed in switching between high-resistive and low-resistive values at the magnetization reversal of the porous system studied.