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1.
Proc Natl Acad Sci U S A ; 121(16): e2400077121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38598345

RESUMO

Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to lower airway repair. Agents that promote the selective expansion of these cells might stimulate regeneration of the compromised alveolar epithelium, an etiology-defining event in several pulmonary diseases. From a high-content imaging screen of the drug repurposing library ReFRAME, we identified that dipeptidyl peptidase 4 (DPP4) inhibitors, widely used type 2 diabetes medications, selectively expand AEC2s and are broadly efficacious in several mouse models of lung damage. Mechanism of action studies revealed that the protease DPP4, in addition to processing incretin hormones, degrades IGF-1 and IL-6, essential regulators of AEC2 expansion whose levels are increased in the luminal compartment of the lung in response to drug treatment. To selectively target DPP4 in the lung with sufficient drug exposure, we developed NZ-97, a locally delivered, lung persistent DPP4 inhibitor that broadly promotes efficacy in mouse lung damage models with minimal peripheral exposure and good tolerability. This work reveals DPP4 as a central regulator of AEC2 expansion and affords a promising therapeutic approach to broadly stimulate regenerative repair in pulmonary disease.


Assuntos
Células Epiteliais Alveolares , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Células Epiteliais Alveolares/metabolismo , Dipeptidil Peptidase 4/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Pulmão/metabolismo , Modelos Animais de Doenças
2.
Mol Cell ; 71(5): 703-717.e9, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30100264

RESUMO

In amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), cytoplasmic aggregates of hyperphosphorylated TDP-43 accumulate and colocalize with some stress granule components, but how pathological TDP-43 aggregation is nucleated remains unknown. In Drosophila, we establish that downregulation of tankyrase, a poly(ADP-ribose) (PAR) polymerase, reduces TDP-43 accumulation in the cytoplasm and potently mitigates neurodegeneration. We establish that TDP-43 non-covalently binds to PAR via PAR-binding motifs embedded within its nuclear localization sequence. PAR binding promotes liquid-liquid phase separation of TDP-43 in vitro and is required for TDP-43 accumulation in stress granules in mammalian cells and neurons. Stress granule localization initially protects TDP-43 from disease-associated phosphorylation, but upon long-term stress, stress granules resolve, leaving behind aggregates of phosphorylated TDP-43. Finally, small-molecule inhibition of Tankyrase-1/2 in mammalian cells inhibits formation of cytoplasmic TDP-43 foci without affecting stress granule assembly. Thus, Tankyrase inhibition antagonizes TDP-43-associated pathology and neurodegeneration and could have therapeutic utility for ALS and FTD.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Animais , Células COS , Linhagem Celular , Núcleo Celular/metabolismo , Chlorocebus aethiops , Citoplasma/metabolismo , Drosophila , Feminino , Degeneração Lobar Frontotemporal/metabolismo , Masculino , Mamíferos/metabolismo , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley
3.
Proc Natl Acad Sci U S A ; 120(18): e2218380120, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37094114

RESUMO

The nature of mass transport in plants has recently inspired the development of low-cost and sustainable wood-based electronics. Herein, we report a wood electrochemical transistor (WECT) where all three electrodes are fully made of conductive wood (CW). The CW is prepared using a two-step strategy of wood delignification followed by wood amalgamation with a mixed electron-ion conducting polymer, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS). The modified wood has an electrical conductivity of up to 69 Sm-1 induced by the formation of PEDOT:PSS microstructures inside the wood 3D scaffold. CW is then used to fabricate the WECT, which is capable of modulating an electrical current in a porous and thick transistor channel (1 mm) with an on/off ratio of 50. The device shows a good response to gate voltage modulation and exhibits dynamic switching properties similar to those of an organic electrochemical transistor. This wood-based device and the proposed working principle demonstrate the possibility to incorporate active electronic functionality into the wood, suggesting different types of bio-based electronic devices.

4.
Proc Natl Acad Sci U S A ; 120(28): e2305085120, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37399395

RESUMO

Chronic cutaneous wounds remain a persistent unmet medical need that decreases life expectancy and quality of life. Here, we report that topical application of PY-60, a small-molecule activator of the transcriptional coactivator Yes-associated protein (YAP), promotes regenerative repair of cutaneous wounds in pig and human models. Pharmacological YAP activation enacts a reversible pro-proliferative transcriptional program in keratinocytes and dermal cells that results in accelerated re-epithelization and regranulation of the wound bed. These results demonstrate that transient topical administration of a YAP activating agent may represent a generalizable therapeutic approach to treating cutaneous wounds.


Assuntos
Qualidade de Vida , Cicatrização , Humanos , Animais , Suínos , Cicatrização/fisiologia , Pele/lesões , Queratinócitos/metabolismo , Administração Cutânea
5.
Proc Natl Acad Sci U S A ; 119(5)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101920

RESUMO

During prolonged trains of presynaptic action potentials (APs), synaptic release reaches a stable level that reflects the speed of replenishment of the readily releasable pool (RRP). Determining the size and filling dynamics of vesicular pools upstream of the RRP has been hampered by a lack of precision of synaptic output measurements during trains. Using the recent technique of tracking vesicular release in single active zone synapses, we now developed a method that allows the sizes of the RRP and upstream pools to be followed in time. We find that the RRP is fed by a small-sized pool containing approximately one to four vesicles per docking site at rest. This upstream pool is significantly depleted by short AP trains, and reaches a steady, depleted state for trains of >10 APs. We conclude that a small, highly dynamic vesicular pool upstream of the RRP potently controls synaptic strength during sustained stimulation.


Assuntos
Potenciais Sinápticos/fisiologia , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/fisiologia , Potenciais de Ação/fisiologia , Animais , Masculino , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/fisiologia , Ratos , Ratos Sprague-Dawley , Sinapses/fisiologia
6.
Proc Natl Acad Sci U S A ; 119(36): e2123201119, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36037360

RESUMO

Using public housing developments as a strategic site, our research documents a distinct pathway linking disadvantaged context to incarceration-the public-housing-to-prison pipeline. Focusing on New York City Housing Authority (NYCHA) housing developments as a case study, we find that incarceration rates in NYCHA tracts are 4.6 times higher than those in non-NYCHA tracts. More strikingly, 94% of NYCHA tracts report rates above the median value for non-NYCHA tracts. Moreover, 17% of New York State's incarcerated population originated from just 372 NYCHA tracts. Compared with non-NYCHA tracts, NYCHA tracts had higher shares of Black residents and were significantly more disadvantaged. This NYCHA disadvantage in concentrated incarceration is also robust at different spatial scales. Our findings have implications for policies and programs to disrupt community-based pipelines to prison.


Assuntos
Prisões , Habitação Popular , População Negra , Humanos , Cidade de Nova Iorque/epidemiologia , Características de Residência , Populações Vulneráveis
7.
Crit Care Med ; 52(2): 258-267, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37909832

RESUMO

OBJECTIVES: Patients at risk of adverse effects related to positive fluid balance could benefit from fluid intake optimization. Less attention is paid to nonresuscitation fluids. We aim to evaluate the heterogeneity of fluid intake at the initial phase of resuscitation. DESIGN: Prospective multicenter cohort study. SETTING: Thirty ICUs across France and one in Spain. PATIENTS: Patients requiring vasopressors and/or invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All fluids administered by vascular or enteral lines were recorded over 24 hours following admission and were classified in four main groups according to their predefined indication: fluids having a well-documented homeostasis goal (resuscitation fluids, rehydration, blood products, and nutrition), drug carriers, maintenance fluids, and fluids for technical needs. Models of regression were constructed to determine fluid intake predicted by patient characteristics. Centers were classified according to tertiles of fluid intake. The cohort included 296 patients. The median total volume of fluids was 3546 mL (interquartile range, 2441-4955 mL), with fluids indisputably required for body fluid homeostasis representing 36% of this total. Saline, glucose-containing high chloride crystalloids, and balanced crystalloids represented 43%, 27%, and 16% of total volume, respectively. Whatever the class of fluids, center of inclusion was the strongest factor associated with volumes. Compared with the first tertile, the difference between the volume predicted by patient characteristics and the volume given was +1.2 ± 2.0 L in tertile 2 and +3.0 ± 2.8 L in tertile 3. CONCLUSIONS: Fluids indisputably required for body fluid homeostasis represent the minority of fluid intake during the 24 hours after ICU admission. Center effect is the strongest factor associated with the volume of fluids. Heterogeneity in practices suggests that optimal strategies for volume and goals of common fluids administration need to be developed.


Assuntos
Estado Terminal , Hidratação , Humanos , Estudos Prospectivos , Estado Terminal/terapia , Estudos de Coortes , Hidratação/efeitos adversos , Soluções Cristaloides , Ressuscitação
8.
PLoS Pathog ; 18(4): e1010012, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35404986

RESUMO

As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled by complex interactions of the fungus and the host to preclude fungal elimination but also fungal overgrowth and invasion, which can result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance of the oral mucosa. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. Using an experimental model of C. albicans oral colonization in mice we explored fungal determinants of commensalism in the oral cavity. Transcript profiling of the oral isolate 101 in the murine tongue tissue revealed a characteristic metabolic profile tailored to the nutrient poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. Here we show that these immune evasive properties of isolate 101 are explained by a strong attenuation of a number of virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of NRG1 abolished the commensal behaviour of isolate 101, thereby establishing a central role of this factor in the commensal lifestyle of C. albicans in the oral niche of the host.


Assuntos
Candida albicans , Candidíase Bucal , Animais , Candidíase Bucal/microbiologia , Proteínas Fúngicas , Camundongos , Mucosa Bucal/microbiologia , Simbiose , Virulência
9.
HIV Med ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443319

RESUMO

INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.

10.
J Med Virol ; 96(2): e29477, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38376942

RESUMO

Human parechovirus A (HPeV-A) is a causative agent of respiratory and gastrointestinal illnesses, acute flaccid paralysis encephalitis, meningitis, and neonatal sepsis. To clarify the characteristics of HPeV-A infection in children, 391 fecal specimens were collected from January 2014 to October 2015 from patients with acute gastroenteritis in Seoul, South Korea. Of these, 221/391 (56.5%) HPeV-A positive samples were found in children less than 2 years old. Three HPeV-A genotypes HPeV-A1 (117/221; 52.94%), HPeV-A3 (100/221; 45.25%), and HPeV-A6 (4/221; 1.81%) were detected, among which HPeV-A3 was predominant with the highest recorded value of 58.6% in 2015. Moreover, recombination events in the Korean HPeV-A3 strains were detected. Phylogenetic analysis revealed that the capsid-encoding regions and noncapsid gene 2A of the four Korean HPeV-A3 strains are closely related to the HPeV-A3 strains isolated in Canada in 2007 (Can82853-01), Japan in 2008 (A308/99), and Taiwan in 2011 (TW-03067-2011) while noncapsid genes P2 (2B-2C) and P3 (3A-3D) are closely related to those of HPeV-A1 strains BNI-788St (Germany in 2008) and TW-71594-2010 (Taiwan in 2010). This first report on the whole-genome analysis of HPeV-A3 in Korea provides insight into the evolving status and pathogenesis of HPeVs in children.


Assuntos
Parechovirus , Criança , Recém-Nascido , Humanos , Pré-Escolar , Filogenia , Parechovirus/genética , República da Coreia/epidemiologia , Evolução Biológica , Recombinação Genética
11.
Hum Reprod ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840410

RESUMO

STUDY QUESTION: In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? SUMMARY ANSWER: In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. WHAT IS KNOWN ALREADY: ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. STUDY DESIGN, SIZE, DURATION: This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). LIMITATIONS, REASONS FOR CAUTION: Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. WIDER IMPLICATIONS OF THE FINDINGS: The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study, and no authors reported conflicting interests. TRIAL REGISTRATION NUMBER: NCT04866524 (clinicaltrials.gov).

12.
Arch Microbiol ; 206(3): 97, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349544

RESUMO

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.


Assuntos
Antineoplásicos , Cordyceps , Neoplasias , Penicillium , Humanos , Penicillium/genética , Carpóforos
13.
EMBO Rep ; 23(8): e54133, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35758160

RESUMO

NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus-infected cells. Given the vast diversity of receptors expressed on NK cells we seek to identify receptors involved in the recognition of HIV-1-infected cells. By combining an unbiased large-scale screening approach with a functional assay, we identify TRAIL to be associated with NK cell degranulation against HIV-1-infected target cells. Further investigating the underlying mechanisms, we demonstrate that TRAIL is able to elicit multiple effector functions in human NK cells independent of receptor-mediated induction of apoptosis. Direct engagement of TRAIL not only results in degranulation but also IFNγ production. Moreover, TRAIL-mediated NK cell activation is not limited to its cognate death receptors but also decoy receptor I, adding a new perspective to the perceived regulatory role of decoy receptors in TRAIL-mediated cytotoxicity. Based on these findings, we propose that TRAIL not only contributes to the anti-HIV-1 activity of NK cells but also possesses a multifunctional role beyond receptor-mediated induction of apoptosis, acting as a regulator for the induction of different effector functions.


Assuntos
Citotoxicidade Imunológica , HIV-1 , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais , Ativação Linfocitária
14.
Rev Med Virol ; 33(5): e2461, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37208958

RESUMO

In 1967, the very first case of the Marburgvirus disease (MVD) was detected in Germany and Serbia sequentially. Since then, MVD has been considered one of the most serious and deadly infectious diseases in the world with a case-fatality rate between 23% and 90% and a substantial number of recorded deaths. Marburgvirus belongs to the family of Filoviridae (filoviruses), which causes severe viral hemorrhagic fever (VHF). Some major risk factors for human infections are close contact with African fruit bats, MVD-infected non-human primates, and MVD-infected individuals. Currently, there is no vaccine or specific treatment for MVD, which emphasizes the seriousness of this disease. In July 2022, the World Health Organization reported outbreaks of MVD in Ghana after two suspected VHF cases were detected. This was followed in February and March 2023 with the emergence of the virus in two countries new to the virus: Equatorial Guinea and Tanzania, respectively. In this review, we aim to highlight the characteristics, etiology, epidemiology, and clinical symptoms of MVD, along with the current prevention measures and the possible treatments to control this virus.


Assuntos
Quirópteros , Ebolavirus , Doença pelo Vírus Ebola , Doença do Vírus de Marburg , Marburgvirus , Animais , Humanos , Doença do Vírus de Marburg/epidemiologia , Doença do Vírus de Marburg/prevenção & controle , Doença do Vírus de Marburg/diagnóstico , Surtos de Doenças , Fatores de Risco
15.
Rev Med Virol ; 33(1): e2398, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150052

RESUMO

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2/genética , Anticorpos Monoclonais , Infecções Irruptivas , Anticorpos Antivirais , Anticorpos Neutralizantes
16.
Public Health Nutr ; : 1-37, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804077

RESUMO

OBJECTIVE: SEANUTS II Vietnam aims to obtain an in-depth understanding of the nutritional status and nutrient intake of children between 0.5-11.9 years old. DESIGN: Cross-sectional survey. SETTING: A multistage cluster systematic random sampling method was implemented in different regions in Vietnam: North Mountainous, Central Highlands, Red River Delta, North Central and Coastal Area, Southeast and Mekong River Delta. PARTICIPANTS: 4001 children between 6 months and 11.9 years of age. RESULTS: Prevalence of stunting and underweight was higher in rural than in urban children, whereas overweight and obese rates were higher in urban areas. 12.0% of the children had anemia and especially children 0.5-1-year-old were affected (38.6%). Low serum retinol was found in 6.2% of children ≥ 4 years old. Prevalence of vitamin D insufficiency was 31.1% while 60.8% had low serum zinc. For nutrient intake, overall, 80.1% of the children did not meet the estimated energy requirements. For calcium intake, ∼60% of the younger children did not meet the RNI while it was 92.6% in children >7 years old. For vitamin D intake, 95.0% of the children did not meet RNI. CONCLUSIONS: SEANUTS II Vietnam indicated that overnutrition was more prevalent than undernutrition in urban areas, while undernutrition was found more in rural areas. The high prevalence of low serum zinc, vitamin D insufficiency and the inadequate intakes of calcium and vitamin D are of concern. Nutrition strategies for Vietnamese children should consider three sides of malnutrition and focus on approaches for the prevention malnutrition.

17.
PLoS Genet ; 17(3): e1009434, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33720931

RESUMO

The conserved fungal velvet family regulatory proteins link development and secondary metabolite production. The velvet domain for DNA binding and dimerization is similar to the structure of the Rel homology domain of the mammalian NF-κB transcription factor. A comprehensive study addressed the functions of all four homologs of velvet domain encoding genes in the fungal life cycle of the soil-borne plant pathogenic fungus Verticillium dahliae. Genetic, cell biological, proteomic and metabolomic analyses of Vel1, Vel2, Vel3 and Vos1 were combined with plant pathogenicity experiments. Different phases of fungal growth, development and pathogenicity require V. dahliae velvet proteins, including Vel1-Vel2, Vel2-Vos1 and Vel3-Vos1 heterodimers, which are already present during vegetative hyphal growth. The major novel finding of this study is that Vel1 is necessary for initial plant root colonization and together with Vel3 for propagation in planta by conidiation. Vel1 is needed for disease symptom induction in tomato. Vel1, Vel2, and Vel3 control the formation of microsclerotia in senescent plants. Vel1 is the most important among all four V. dahliae velvet proteins with a wide variety of functions during all phases of the fungal life cycle in as well as ex planta.


Assuntos
Proteínas Fúngicas/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Esporos Fúngicos , Verticillium/fisiologia , Xilema/metabolismo , Proteínas de Ligação a DNA , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Interações Hospedeiro-Patógeno , Solanum lycopersicum , Modelos Biológicos , Fenótipo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Metabolismo Secundário
18.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34535550

RESUMO

Sex strongly impacts genome evolution via recombination and segregation. In the absence of these processes, haplotypes within lineages of diploid organisms are predicted to accumulate mutations independently of each other and diverge over time. This so-called "Meselson effect" is regarded as a strong indicator of the long-term evolution under obligate asexuality. Here, we present genomic and transcriptomic data of three populations of the asexual oribatid mite species Oppiella nova and its sexual relative Oppiella subpectinata We document strikingly different patterns of haplotype divergence between the two species, strongly supporting Meselson effect-like evolution and long-term asexuality in O. nova: I) variation within individuals exceeds variation between populations in O. nova but vice versa in O. subpectinata; II) two O. nova sublineages feature a high proportion of lineage-specific heterozygous single-nucleotide polymorphisms (SNPs), indicating that haplotypes continued to diverge after lineage separation; III) the deepest split in gene trees generally separates the two haplotypes in O. nova, but populations in O. subpectinata; and IV) the topologies of the two haplotype trees match each other. Our findings provide positive evidence for the absence of canonical sex over evolutionary time in O. nova and suggest that asexual oribatid mites can escape the dead-end fate usually associated with asexual lineages.


Assuntos
Ácaros/genética , Reprodução Assexuada/genética , Ácaros e Carrapatos/genética , Animais , Evolução Molecular , Variação Genética/genética , Haplótipos/genética , Filogenia
19.
J Fish Dis ; : e13935, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403934

RESUMO

Acute Hepatopancreatic Necrosis Disease (AHPND) represents a significant challenge in the field of shrimp aquaculture. This disease is primarily caused by Vibrio parahaemolyticus strains harbouring the pVA1 plasmid encoding the PirAvp and PirBvp toxins. To combat this epidemic and mitigate its devastating consequences, it is crucial to identify and characterize the receptors responsible for the binding of these pathogenic toxins. Our studied discovered that Penaeus vannamei's Serine protease inhibitor 3 (PvSerpin3) derived from shrimp hepatopancreatic tissues could bind to recombinant PirAvp , confirming its role as a novel PirAvp -binding protein (PA BP). Through comprehensive computational methods, we revealed two truncated PirAvp -binding proteins derived from PvSerpin3 called Serpin3(13) and Serpin3(22), which had higher affinity to PirAvp than the full-length PvSerpin3. The PA BP genes were amplified from a cDNA library that was reversed from total RNA extracted from shrimp, cloned and expressed in Escherichia coli. Three PA BP inclusion bodies were refolded to obtain the soluble form, and the recovery efficacy was found to be 100% for Serpin3 and Serpin3(13), while Serpin3(22) had a recovery efficacy of roundly 50%. Co-Immunoprecipitation (co-IP) and dot blot assays substantiated the interaction of these recombinant PA BPs with both recombinant PirAvp and VPAHPND (XN89)-producing natural toxins.

20.
Molecules ; 29(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893443

RESUMO

Although disubstituted imidazolium cation is sterically crowded, hundreds of ionic liquids based on this cation have been reported as electrolytes for energy storage devices. In contrast to disubstituted imidazolium, non-substituted imidazolium is uncrowded sterically and has not yet been investigated as an electrolyte, to the best of our knowledge. Hence, imidazolium hydrogen sulfate [Imi][HSO4], in mixture with water, was studied as an electrolyte for PANI-based electrode materials. For comparison, pyrrolidinium with hydrogen sulfate or p-toluene sulfonate ([Pyrr][HSO4] or [Pyrr][PTS]), in mixture with water, were also investigated as alternatives to the conventional electrolyte (i.e., aqueous H2SO4) for PANI electrodes. Walden plots of binary mixture ionic liquid-water weight ratios with the optimal ionic conductivity (i.e., [Imi][HSO4]/water 48/52 wt% (195.1 mS/cm), [Pyrr][HSO4]/water 41/59 wt% (186.6 mS/cm), and [Pyrr][PTS]/water 48/52 wt% (43.4 mS/cm) along with the electrochemical performances of PANI in these binary mixtures showed that [Pyrr][HSO4]aq or [Imi][HSO4]aq are convenient electrolytes for PANI/PIL, as opposed to [Pyrr][PTS]aq. Furthermore, replacing the conventional aqueous electrolyte H2SO4 with [Imi][HSO4] aq increased the specific capacitance of PANI/PIL from 249.8 to 268.5 F/g at 15 mV/s. Moreover, PANI/PIL electrodes displayed a quasi-ideal capacitive behavior in [Imi][HSO4]aq (the correction factor of CPE4 was 0.99). This primary study has shown that non-substituted imidazolium as an electrolyte could enhance the electrochemical performances of PANI electrodes and could be a good alternative to the conventional electrolyte.

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