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1.
Beilstein J Org Chem ; 20: 2401-2407, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355855

RESUMEN

Diaryliodonium(III) salts have been established as powerful halogen-bond donors in recent years. Herein, a new structural motif for this compound class was developed: iodoloisoxazolium salts, bearing a cyclic five-membered iodolium core fused with an isoxazole ring. A derivative of this class was synthesized and investigated in the solid state by X-ray crystallography. Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide.

2.
Biomolecules ; 14(9)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39334955

RESUMEN

Cystic fibrosis (CF) is a hereditary disease characterized by the progression of respiratory disorders, especially in adult patients. The purpose of the study was to identify volatile organic compounds (VOCs) as predictors of respiratory dysfunction, chronic respiratory infections of Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, and VOCs associated with severe genotype and highly effective modulator treatment (HEMT). Exhaled breath samples from 102 adults with CF were analyzed using PTR-TOF-MS, obtained during a forced expiratory maneuver and normal quiet breathing. Using cross-validation and building gradient boosting classifiers (XGBoost), the importance of VOCs for functional and clinical outcomes was determined. The presence of the previously identified VOCs indole, phenol, and dimethyl sulfide were metabolic outcomes associated with impaired respiratory function. New VOCs associated with respiratory disorders were methyl acetate, carbamic acid, 1,3-Pentadiene, and 2,3-dimethyl-2-butene; VOCs associated with the above mentioned respiratory pathogens were non-differentiable nitrogen-containing organic compounds m/z = 47.041 (CH5NO)+ and m/z = 44.044 (C2H5NH+), hydrocarbons (cyclopropane, propene) and methanethiol; and VOCs associated with severe CFTR genotype were non-differentiable VOC m/z = 281.053. No significant features associated with the use of HEMT were identified. Early non-invasive determination of VOCs as biomarkers of the severity of CF and specific pathogenic respiratory flora could make it possible to prescribe adequate therapy and assess the prognosis of the disease. However, further larger standardized studies are needed for clinical use.


Asunto(s)
Pruebas Respiratorias , Fibrosis Quística , Espectrometría de Masas , Compuestos Orgánicos Volátiles , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/metabolismo , Adulto , Femenino , Masculino , Pruebas Respiratorias/métodos , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Espectrometría de Masas/métodos , Espiración , Adulto Joven , Persona de Mediana Edad , Protones , Biomarcadores/metabolismo
3.
JAMA Netw Open ; 7(8): e2430205, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39186266

RESUMEN

Importance: Department of Veterans Affairs (VA) health care spending has increased in the past decade, in part due to legislative changes that expanded access to VA-purchased care. Objective: To understand how insurance coverage and enrollment in VA has changed between 2010 and 2021. Design, Setting, and Participants: This cross-sectional study used data from surveys conducted from 2010 to 2021. Participants were respondents across 4 national surveys who reported being a US veteran and reported on health insurance enrollment. Data were analyzed from October 2023 to June 2024. Main Outcomes and Measures: Self-reported health insurance coverage, reliance on VA insurance, and self-reported health. Results: Among a total of 3 644 614 survey respondents (mean [SE] age, 60 [0.04] years; 91.3% [95% CI, 91.2%-91.5%] male) included, 52.2% (95% CI, 52.0%-52.4%) were out of the labor market and 63.1% (95% CI, 62.9%-63.3%) were married. In 2010, 94% of all veterans and 94% of veterans younger than age 65 years reported having health insurance coverage on the American Community Survey. Insurance enrollment increased over time, and by 2020, 97% of all veterans and 95% of veterans younger than 65 years reported having health insurance coverage on the American Community Survey. Insurance enrollment estimates were similar across the surveys. Approximately one-third of veterans reported being enrolled in VA health coverage. Of those who enrolled in VA insurance, more than 75% had more than 1 form of coverage, with Medicare and private insurance being the most common second insurance sources. VA insurance enrollment was negatively associated with income and health status. Veterans without insurance tended to be unemployed and younger. Conclusions and Relevance: This study of veterans who responded to 4 national surveys found that veterans enrolled in VA health coverage had high rates of dual coverage. Further legislative efforts to increase access without recognizing the high rates of dual coverage may yield unintended consequences, such payer shifting.


Asunto(s)
Cobertura del Seguro , Seguro de Salud , Veteranos , Humanos , Estados Unidos , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Veteranos/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Cobertura del Seguro/estadística & datos numéricos , Cobertura del Seguro/tendencias , Anciano , United States Department of Veterans Affairs/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios
4.
Acta Crystallogr D Struct Biol ; 80(Pt 8): 599-604, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38984904

RESUMEN

The Azotobacter vinelandii FeSII protein forms an oxygen-resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin-type ferredoxin that forms a dimer in solution. Previously, the crystal structure was solved [Schlesier et al. (2016), J. Am. Chem. Soc. 138, 239-247] with five copies in the asymmetric unit. One copy is a normal adrenodoxin domain that forms a dimer with its crystallographic symmetry mate. The other four copies are in an `open' conformation with a loop flipped out exposing the 2Fe-2S cluster. The open and closed conformations were interpreted as oxidized and reduced, respectively, and the large conformational change in the open configuration allowed binding to nitrogenase. Here, the structure of FeSII was independently solved in the same crystal form. The positioning of the atoms in the unit cell is similar to the earlier report. However, the interpretation of the structure is different. The `open' conformation is interpreted as the product of a crystallization-induced domain swap. The 2Fe-2S cluster is not exposed to solvent, but in the crystal its interacting helix is replaced by the same helix residues from a crystal symmetry mate. The domain swap is complicated, as it is unusual in being in the middle of the protein rather than at a terminus, and it creates arrangements of molecules that can be interpreted in multiple ways. It is also cautioned that crystal structures should be interpreted in terms of the contents of the entire crystal rather than of one asymmetric unit.


Asunto(s)
Azotobacter vinelandii , Proteínas Bacterianas , Modelos Moleculares , Azotobacter vinelandii/química , Cristalografía por Rayos X , Proteínas Bacterianas/química , Conformación Proteica , Dominios Proteicos , Ferredoxinas/química , Multimerización de Proteína , Proteínas Hierro-Azufre/química
5.
PLoS Pathog ; 20(7): e1011910, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39024231

RESUMEN

The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans and swine. Swine have many physiological, anatomical, and immunological similarities to humans, and are an excellent model for human influenza. Here, we employed single cell RNA-sequencing (scRNA-seq) and flow cytometry to characterize the major leukocyte subsets in bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with an adenoviral vector vaccine expressing hemagglutinin and nucleoprotein with or without IL-1ß. Mapping scRNA-seq clusters from BAL onto those previously described in peripheral blood facilitated annotation and highlighted differences between tissue resident and circulating immune cells. ScRNA-seq data and functional assays revealed lasting impacts of immune challenge on BAL populations. First, mucosal administration of IL-1ß reduced the number of functionally active Treg cells. Second, influenza infection upregulated IFI6 in BAL cells and decreased their susceptibility to virus replication in vitro. Our data provide a reference map of porcine BAL cells and reveal lasting immunological consequences of influenza infection and respiratory immunization in a highly relevant large animal model for respiratory virus infection.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Pulmón , Infecciones por Orthomyxoviridae , Análisis de la Célula Individual , Animales , Porcinos , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Pulmón/inmunología , Pulmón/virología , Vacunas contra la Influenza/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Inmunización , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virología
6.
Pediatr Emerg Care ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39051988

RESUMEN

OBJECTIVES: Simulating a realistic "cannot intubate, cannot oxygenate" (CICO) situation to train an "emergency front of neck airway" is difficult. It further remains unclear if provision of regular technical refreshers improves performance in the setting of a real CICO situation. The purpose of this prospective study on an established surgical rabbit cadaver tracheostomy model was to evaluate the benefit of viewing training material shortly before performing "emergency front of neck airway." METHODS: Previously trained participants were randomized into 2 groups. The control group (video) was allowed to watch an instructional video before performing a tracheotomy on the training model, while the study group (nonvideo) was not. Queried outcomes included success rate, performance time, and severe secondary airway injuries between the 2 groups. RESULTS: In 29 tracheotomies performed by 29 participants, the overall success rate was 86% (92% video; 81% nonvideo, P = 0.4). Performance time was not different between the 2 groups (video: 80 s [IQR25-75: 53-86], nonvideo 64 s [IQR25-75: 47-102]; P = 0.93). Only in the nonvideo group, the performance time and the time between the workshops correlated positively (P = 0.048). Severe secondary injuries were noted in 4 of 29 rabbit cadavers, 2 in each group. Watching a refresher video before performing an emergency surgical tracheostomy in an infant training model did not influence the success rate and the performance time in previously trained anesthetists. CONCLUSIONS: These results highlight the ease of learning, memorization, and recall of this emergency surgical tracheostomy technique and may demonstrate its applicability in a real infant CICO situation.

7.
Front Immunol ; 15: 1376395, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38975350

RESUMEN

Influenza A Virus (IAV) and Respiratory Syncytial Virus (RSV) are both responsible for millions of severe respiratory tract infections every year worldwide. Effective vaccines able to prevent transmission and severe disease, are important measures to reduce the burden for the global health system. Despite the strong systemic immune responses induced upon current parental immunizations, this vaccination strategy fails to promote a robust mucosal immune response. Here, we investigated the immunogenicity and efficacy of a mucosal adenoviral vector vaccine to tackle both pathogens simultaneously at their entry site. For this purpose, BALB/c mice were immunized intranasally with adenoviral vectors (Ad) encoding the influenza-derived proteins, hemagglutinin (HA) and nucleoprotein (NP), in combination with an Ad encoding for the RSV fusion (F) protein. The mucosal combinatory vaccine induced neutralizing antibodies as well as local IgA responses against both viruses. Moreover, the vaccine elicited pulmonary CD8+ and CD4+ tissue resident memory T cells (TRM) against the immunodominant epitopes of RSV-F and IAV-NP. Furthermore, the addition of Ad-TGFß or Ad-CCL17 as mucosal adjuvant enhanced the formation of functional CD8+ TRM responses against the conserved IAV-NP. Consequently, the combinatory vaccine not only provided protection against subsequent infections with RSV, but also against heterosubtypic challenges with pH1N1 or H3N2 strains. In conclusion, we present here a potent combinatory vaccine for mucosal applications, which provides protection against two of the most relevant respiratory viruses.


Asunto(s)
Anticuerpos Antivirales , Inmunidad Mucosa , Virus de la Influenza A , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Animales , Ratones , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Femenino , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Virus Sincitiales Respiratorios/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Humanos , Adenoviridae/inmunología , Adenoviridae/genética , Vectores Genéticos
8.
J Immunother Cancer ; 12(3)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38458636

RESUMEN

BACKGROUND: Generally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome. METHODS: Here, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1ß to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model. RESULTS: The mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice. CONCLUSION: In summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Pulmonares , Animales , Ratones , Antígenos de Neoplasias , Memoria Inmunológica , Vacunación , Vacunas contra el Cáncer/uso terapéutico , Neoplasias Pulmonares/terapia
9.
bioRxiv ; 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37873405

RESUMEN

The balance between mitochondrial calcium (mCa2+) uptake and efflux regulates ATP production, but if perturbed causes energy starvation or mCa2+ overload and cell death. The mitochondrial sodium-calcium exchanger, NCLX, is a critical route of mCa2+ efflux in excitable tissues, such as the heart and brain, and animal models support NCLX as a promising therapeutic target to limit pathogenic mCa2+ overload. However, the mechanisms that regulate NCLX activity remain largely unknown. We used proximity biotinylation proteomic screening to identify the NCLX interactome and define novel regulators of NCLX function. Here, we discover the mitochondrial inner membrane protein, TMEM65, as an NCLX-proximal protein that potently enhances sodium (Na+)-dependent mCa2+ efflux. Mechanistically, acute pharmacologic NCLX inhibition or genetic deletion of NCLX ablates the TMEM65-dependent increase in mCa2+ efflux. Further, loss-of-function studies show that TMEM65 is required for Na+-dependent mCa2+ efflux. Co-fractionation and in silico structural modeling of TMEM65 and NCLX suggest these two proteins exist in a common macromolecular complex in which TMEM65 directly stimulates NCLX function. In line with these findings, knockdown of Tmem65 in mice promotes mCa2+ overload in the heart and skeletal muscle and impairs both cardiac and neuromuscular function. We further demonstrate that TMEM65 deletion causes excessive mitochondrial permeability transition, whereas TMEM65 overexpression protects against necrotic cell death during cellular Ca2+ stress. Collectively, our results show that loss of TMEM65 function in excitable tissue disrupts NCLX-dependent mCa2+ efflux, causing pathogenic mCa2+ overload, cell death and organ-level dysfunction, and that gain of TMEM65 function mitigates these effects. These findings demonstrate the essential role of TMEM65 in regulating NCLX-dependent mCa2+ efflux and suggest modulation of TMEM65 as a novel strategy for the therapeutic control of mCa2+ homeostasis.

10.
Ecol Evol ; 13(9): e10524, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37720058

RESUMEN

The pteromalid parasitoid Lariophagus distinguendus (Foerster) belongs to the Hymenoptera, a megadiverse insect order with high cryptic diversity. It attacks stored product pest beetles in human storage facilities. Recently, it has been shown to consist of two separate species. To further study its cryptic diversity, strains were collected to compare their relatedness using barcoding and nuclear genes. Nuclear genes identified two clusters which agree with the known two species, whereas the barcode fragment determined an additional third Clade. Total reproductive isolation (RI) according to the biological species concept (BSC) was investigated in crossing experiments within and between clusters using representative strains. Sexual isolation exists between all studied pairs, increasing from slight to strong with genetic distance. Postzygotic barriers mostly affected hybrid males, pointing to Haldane's rule. Hybrid females were only affected by unidirectional Spiroplasma-induced cytoplasmic incompatibility and behavioural sterility, each in one specific strain combination. RI was virtually absent between strains separated by up to 2.8% COI difference, but strong or complete in three pairs from one Clade each, separated by at least 7.2%. Apparently, each of these clusters represents one separate species according to the BSC, highlighting cryptic diversity in direct vicinity to humans. In addition, these results challenge the recent 'turbo-taxonomy' practice of using 2% COI differences to delimitate species, especially within parasitic Hymenoptera. The gradual increase in number and strength of reproductive barriers between strains with increasing genetic distance also sheds light on the emergence of barriers during the speciation process in L. distinguendus.

11.
JAMA Netw Open ; 6(7): e2323884, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37459100

RESUMEN

This cross-sectional study using survey data investigates the association between level of reliance on the Department of Veterans Affairs for health care and self-reported health by type of insurance coverage among VA enrollees.


Asunto(s)
Veteranos , Humanos , Estados Unidos , Autoinforme , Atención a la Salud , Aceptación de la Atención de Salud , United States Department of Veterans Affairs
12.
Front Immunol ; 14: 1181716, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153548

RESUMEN

T cell responses directed against highly conserved viral proteins contribute to the clearance of the influenza virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses in mice and ferrets. We examined the protective efficacy of mucosal delivery of adenoviral vectors expressing hemagglutinin (HA) and nucleoprotein (NP) from the H1N1 virus against heterologous H3N2 challenge in pigs. We also evaluated the effect of mucosal co-delivery of IL-1ß, which significantly increased antibody and T cell responses in inbred Babraham pigs. Another group of outbred pigs was first exposed to pH1N1 as an alternative means of inducing heterosubtypic immunity and were subsequently challenged with H3N2. Although both prior infection and adenoviral vector immunization induced strong T-cell responses against the conserved NP protein, none of the treatment groups demonstrated increased protection against the heterologous H3N2 challenge. Ad-HA/NP+Ad-IL-1ß immunization increased lung pathology, although viral load was unchanged. These data indicate that heterotypic immunity may be difficult to achieve in pigs and the immunological mechanisms may differ from those in small animal models. Caution should be applied in extrapolating from a single model to humans.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Animales , Humanos , Adyuvantes Inmunológicos , Anticuerpos Antivirales , Subtipo H3N2 del Virus de la Influenza A , Porcinos
13.
Nature ; 618(7964): 328-332, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37138083

RESUMEN

Artefacts made from stones, bones and teeth are fundamental to our understanding of human subsistence strategies, behaviour and culture in the Pleistocene. Although these resources are plentiful, it is impossible to associate artefacts to specific human individuals1 who can be morphologically or genetically characterized, unless they are found within burials, which are rare in this time period. Thus, our ability to discern the societal roles of Pleistocene individuals based on their biological sex or genetic ancestry is limited2-5. Here we report the development of a non-destructive method for the gradual release of DNA trapped in ancient bone and tooth artefacts. Application of the method to an Upper Palaeolithic deer tooth pendant from Denisova Cave, Russia, resulted in the recovery of ancient human and deer mitochondrial genomes, which allowed us to estimate the age of the pendant at approximately 19,000-25,000 years. Nuclear DNA analysis identifies the presumed maker or wearer of the pendant as a female individual with strong genetic affinities to a group of Ancient North Eurasian individuals who lived around the same time but were previously found only further east in Siberia. Our work redefines how cultural and genetic records can be linked in prehistoric archaeology.


Asunto(s)
Huesos , ADN Antiguo , Diente , Animales , Femenino , Humanos , Arqueología/métodos , Huesos/química , Ciervos/genética , ADN Antiguo/análisis , ADN Antiguo/aislamiento & purificación , ADN Mitocondrial/análisis , ADN Mitocondrial/aislamiento & purificación , Historia Antigua , Siberia , Diente/química , Cuevas , Federación de Rusia
14.
Carcinogenesis ; 44(1): 46-53, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-36661216

RESUMEN

This research is relevant, as AL-amyloidosis refers to a systemic type of disease characterized by aggregation of an improperly folded light chain of an immunoglobulin, mainly in the heart and kidneys, causing organ failure. This study describes the clinical experience of introducing a patient with cardiac amyloidosis associated with multiple myeloma (MM). A clinical case of a patient diagnozed with amyloidosis was considered. Magnetic resonance imaging signs of cardiac amyloidosis were confirmed due to the presence of concentric biventricular hypertrophy without dilation, atrial septal hypertrophy, a tendency to atrial dilation, thickening of valve flaps and atrial walls. Upon admission to the research institute, the patient had an anasarca. More accurate recognition of AL-amyloidosis by cardiologists allows for prescribing earlier treatment and improving results. Conventional treatment of MM and AL-amyloidosis includes a combination of dexamethasone with bortezomib and endoxan. Haematopoietic stem cell transplantation after taking high doses of melphalan has become another treatment option and has led to remission in some patients. The novelty of the study is that an example of a timely complete diagnosis and treatment of a combination of these two diseases was presented, as a result of which the patient has achieved a complete haematological and partial organ response to the underlying disease.


Asunto(s)
Amiloidosis , Fibrilación Atrial , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Mieloma Múltiple , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Amiloidosis/tratamiento farmacológico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Hipertrofia/complicaciones , Resultado del Tratamiento
15.
Environ Sci Pollut Res Int ; 30(1): 407-419, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35900624

RESUMEN

Freshwater grazers are suitable organisms to investigate the fate of environmental pollutants, such as weathered multi-walled carbon nanotubes (wMWCNTs). One key process is the uptake of ingested materials into digestive or absorptive cells. To address this, we investigated the localization of wMWCNTs in the intestinal tracts of the mud snail Lymnaea stagnalis (L. stagnalis) and the mayfly Rhithrogena semicolorata (R. semicolorata). In L. stagnalis, bundles of wMWCNTs could be detected in the midgut lumen, whereas only single wMWCNTs could be detected in the lumina of the digestive gland. Intracellular uptake of wMWCNTs was detected by transmission electron microscopy (TEM) but was restricted to the cells of the digestive gland. In larvae of R. semicolorata, irritations of the microvilli and damages in the apical parts of the epithelial gut cells were detected after feeding with 1 to 10 mg/L wMWCNTs. In both models, we detected fibrillar structures in close association with the epithelial cells that formed peritrophic membranes (PMs). The PM may cause a reduced transmission of wMWCNT bundles into the epithelium by forming a filter barrier and potentially protecting the cells from the wMWCNTs. As a result, the uptake of wMWCNTs into cells is rare in mud snails and may not occur at all in mayfly larvae. In addition, we monitor physiological markers such as levels of glycogen or triglycerides and the RNA/DNA ratio. This ratio was significantly affected in L. stagnalis after 24 days with 10 mg/L wMWCNTs, but not in R. semicolorata after 28 days and 10 mg/L wMWCNTs. However, significant effects on the energy status of R. semicolorata were analysed after 28 days of exposure to 1 mg/L wMWCNTs. Furthermore, we observed a significant reduction of phagosomes per enterocyte cell in mayfly larvae at a concentration of 10 mg/L wMWCNTs (p < 0.01).


Asunto(s)
Ephemeroptera , Nanotubos de Carbono , Animales , Lymnaea/fisiología , Larva , Células Epiteliales , Agua Dulce
17.
NTM ; 30(4): 501-527, 2022 12.
Artículo en Alemán | MEDLINE | ID: mdl-36322167

RESUMEN

In March 1986, a public symposium took place in Heidelberg about the "unresolved potential dangers of genetic engineering". The event was organized by institutions affiliated with the environmental movement. Choosing this symposium as an example, the article shows how the public appearance of scientists can be understood as a form of political activism. The article shows how specialists from fields as diverse as biology, chemistry, physics, law and political sciences tried to place political messages by putting themselves in the limelight as independent scientists. I argue that the symposium was both: a place of science communication intertwined with political agitation that, as should be noted, happened in a time when the West German government was working on the legislation of genetic engineering, legitimated by relying on independent expertise. It can be concluded that the discourse of scientific independence became a strategic tool in the controversial debate about the uses and dangers of genetic engineering. Thus, it draws attention to a dimension of political-scientific activity which cannot be fully grasped by the concept of 'the expert' that is established in the history of science.


Asunto(s)
Ingeniería Genética , Política , Historia del Siglo XX , Gobierno , Física , Comunicación
18.
Nature ; 610(7932): 519-525, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36261548

RESUMEN

Genomic analyses of Neanderthals have previously provided insights into their population history and relationship to modern humans1-8, but the social organization of Neanderthal communities remains poorly understood. Here we present genetic data for 13 Neanderthals from two Middle Palaeolithic sites in the Altai Mountains of southern Siberia: 11 from Chagyrskaya Cave9,10 and 2 from Okladnikov Cave11-making this one of the largest genetic studies of a Neanderthal population to date. We used hybridization capture to obtain genome-wide nuclear data, as well as mitochondrial and Y-chromosome sequences. Some Chagyrskaya individuals were closely related, including a father-daughter pair and a pair of second-degree relatives, indicating that at least some of the individuals lived at the same time. Up to one-third of these individuals' genomes had long segments of homozygosity, suggesting that the Chagyrskaya Neanderthals were part of a small community. In addition, the Y-chromosome diversity is an order of magnitude lower than the mitochondrial diversity, a pattern that we found is best explained by female migration between communities. Thus, the genetic data presented here provide a detailed documentation of the social organization of an isolated Neanderthal community at the easternmost extent of their known range.


Asunto(s)
Hombre de Neandertal , Animales , Femenino , Humanos , Cuevas , Genoma/genética , Hibridación Genética , Hombre de Neandertal/genética , Siberia , ADN Mitocondrial/genética , Cromosoma Y/genética , Masculino , Familia , Homocigoto
19.
Front Immunol ; 13: 898690, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860249

RESUMEN

Background: Inflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation to decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients with recent acute coronary syndrome and chronic coronary disease. However, the biological basis of these observations remains elusive. We sought to explore the mechanism by which colchicine beneficially alters the course of atherosclerosis. Methods and Results: In mice with early atherosclerosis (Apoe-/- mice on a high cholesterol diet for 8 weeks), we found that colchicine treatment (0.25 mg/kg bodyweight once daily over four weeks) reduced numbers of neutrophils, inflammatory monocytes and macrophages inside atherosclerotic aortas using flow cytometry and immunohistochemistry. Consequently, colchicine treatment resulted in a less inflammatory plaque composition and reduced plaque size. We next investigated how colchicine prevented plaque leukocyte expansion and found that colchicine treatment mitigated recruitment of blood neutrophils and inflammatory monocytes to plaques as revealed by adoptive transfer experiments. Causally, we found that colchicine reduced levels of both leukocyte adhesion molecules and receptors for leukocyte chemoattractants on blood neutrophils and monocytes. Further experiments showed that colchicine treatment reduced vascular inflammation also in post-myocardial infarction accelerated atherosclerosis through similar mechanisms as documented in early atherosclerosis. When we examined whether colchicine also decreased numbers of macrophages inside atherosclerotic plaques by impacting monocyte/macrophage transitioning or in-situ proliferation of macrophages, we report that colchicine treatment did not influence macrophage precursor differentiation or macrophage proliferation using cell culture experiments with bone marrow derived macrophages. Conclusions: Our data reveal that colchicine prevents expansion of plaque inflammatory leukocytes through lowering recruitment of blood myeloid cells to plaques. These data provide novel mechanistic clues on the beneficial effects of colchicine in the treatment of atherosclerosis and may inform future anti-inflammatory interventions in patients at risk.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Aterosclerosis/prevención & control , Colchicina/farmacología , Colchicina/uso terapéutico , Inflamación/prevención & control , Leucocitos , Ratones , Placa Aterosclerótica/tratamiento farmacológico
20.
Microbiologyopen ; 11(3): e1299, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35765181

RESUMEN

As a hallmark of Archaea, their cell membranes are comprised of ether lipids. However, Archaea-type ether lipids have recently been identified in Bacteria as well, with a somewhat different composition: In Bacillales, sn-glycerol 1-phosphate is etherified with one C35 isoprenoid chain, which is longer than the typical C20 chain in Archaea, and instead of a second isoprenoid chain, the product heptaprenylglyceryl phosphate becomes dephosphorylated and afterward diacetylated by the O-acetyltransferase YvoF. Interestingly, database searches have revealed YvoF homologs in Halobacteria (Archaea), too. Here, we demonstrate that YvoF from Haloferax volcanii can acetylate geranylgeranylglycerol in vitro. Additionally, we present the first-time identification of acetylated diether lipids in H. volcanii and Halobacterium salinarum by mass spectrometry. A variety of different acetylated lipids, namely acetylated archaeol, and acetylated archaetidylglycerol, were found, suggesting that halobacterial YvoF has a broad substrate range. We suppose that the acetyl group might serve to modify the polarity of the lipid headgroup, with still unknown biological effects.


Asunto(s)
Archaea , Bacillales , Archaea/metabolismo , Éteres/química , Éteres/metabolismo , Espectrometría de Masas , Terpenos/metabolismo
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