Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.489
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
Nat Commun ; 15(1): 9210, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39468043

RESUMO

Courtship interactions are remarkably diverse in form and complexity among species. How neural circuits evolve to encode new behaviors that are functionally integrated into these dynamic social interactions is unknown. Here we report a recently originated female sexual behavior in the island endemic Drosophila species D. santomea, where females signal receptivity to male courtship songs by spreading their wings, which in turn promotes prolonged songs in courting males. Copulation success depends on this female signal and correlates with males' ability to adjust his singing in such a social feedback loop. Functional comparison of sexual circuitry across species suggests that a pair of descending neurons, which integrates male song stimuli and female internal state to control a conserved female abdominal behavior, drives wing spreading in D. santomea. This co-option occurred through the refinement of a pre-existing, plastic circuit that can be optogenetically activated in an outgroup species. Combined, our results show that the ancestral potential of a socially-tuned key circuit node to engage the wing motor circuit facilitates the expression of a new female behavior in appropriate sensory and motivational contexts. More broadly, our work provides insights into the evolution of social behaviors, particularly female behaviors, and the underlying neural mechanisms.


Assuntos
Corte , Drosophila , Comportamento Sexual Animal , Asas de Animais , Animais , Feminino , Comportamento Sexual Animal/fisiologia , Masculino , Drosophila/fisiologia , Asas de Animais/fisiologia , Copulação/fisiologia , Evolução Biológica , Neurônios/fisiologia , Optogenética , Vias Neurais/fisiologia
2.
J Phys Chem B ; 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39473385

RESUMO

Weak nonspecific interactions between biomacromolecules determine the cytoplasmic organization. Despite their importance, it is challenging to determine these interactions in the intracellular dense and heterogeneous mixture of biomacromolecules. Here, we develop a method to indicate electrostatic and hydrophobic associative interactions and map these interactions. The method relies on a genetically encoded probe containing a sensing peptide and a circularly permuted green fluorescent protein that provides a ratiometric readout. Inside bacterial and mammalian cells, we see that the cytoplasmic components interact strongly with cationic and hydrophobic probes but not with neutral hydrophilic probes, which remain inert. The Escherichia coli cytoplasm interacts strongly with highly negatively charged hydrophilic probes, but the HEK293T cytoplasm does not. These associative interactions are modulated by ATP depletion. Hence, the nonspecific associative interaction profile in cells is condition- and species-dependent.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39309546

RESUMO

The incidence of diseases caused by pathogens transmitted by the tick Ixodes ricinus vary over time and space through incompletely understood mechanisms. An important determinant of the disease risk is the density of infected ticks, which is the infection prevalence times the density of questing ticks. We therefore investigated the spatial and temporal variation of four pathogens and one of the most abundant symbionts in Ixodes ricinus in questing nymphs over four years of monthly collections in 12 locations in the Netherlands. The infection prevalence of all microbes showed markedly different patterns with significant spatial variation for Borrelia burgdorferi (s.l.), Neoehrlichia mikurensis, Rickettsia helvetica, and Midichloria mitochondrii, significant seasonal variation of B. burgdorferi (s.l.), N. mikurensis, and M. mitochondrii and a significant interannual variation of R. helvetica. Despite its ubiquitous presence, no spatio-temporal variation was observed for the infection prevalence of B. miyamotoi. The variation in infection prevalence was generally smaller than the variation in the density of nymphs, which fluctuated substantially both seasonally and between locations. This means that the variation in the densities of infected nymphs for all pathogens was mostly the result of the variation in densities of nymphs. We also investigated whether there were positive or negative associations between the symbionts, and more specifically whether ticks infected with vertically transmitted symbionts like M. mitochondrii and R. helvetica, have a higher prevalence of horizontally transmitted symbionts, such as B. burgdorferi (s.l.) and N. mikurensis. We indeed found a clear positive association between M. mitochondrii and B. burgdorferi (s.l.). The positive association between R. helvetica and B. burgdorferi (s.l.) was less clear and was only shown in two locations. Additionally, we found a clear positive association between B. burgdorferi (s.l.) and N. mikurensis, which are both transmitted by rodents. Our longitudinal study indicated strong between-location variation, some seasonal patterns and hardly any differences between years for most symbionts. Positive associations between symbionts were observed, suggesting that infection with a (vertically transmitted) symbiont may influence the probability of infection with other symbionts, or that there is a common underlying mechanism (e.g. feeding on rodents).

4.
J Pediatr ; 276: 114325, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39343131

RESUMO

OBJECTIVES: To assess clinical and electroencephalogram (EEG) predictors of epilepsy and to describe the percentage of electrographic seizures and development of epilepsy among patients with spontaneous intracerebral hemorrhage (ICH) due to arteriovenous malformation (AVM) rupture. STUDY DESIGN: Retrospective review of patients admitted to the pediatric intensive care unit with ICH secondary to AVM rupture over 11 years. Clinical variables were collected by review of the electronic medical record. Seizures were described as acute symptomatic (7 days after AVM rupture), subacute (7-30 days after AVM rupture) and remote (greater than 30 days after AVM rupture). Outcome metrics included mortality, and the development of epilepsy post discharge. Descriptive statistics were used. RESULTS: Forty-three patients met inclusion criteria with a median age of 12.2 years (IQR 7.3-14.8) and 49% (21/43) were female. Sixteen percent (7/43) presented with a clinical seizure prior to EEG placement. EEG was performed in 62% (27/43) of patients; one had electrographic status epilepticus without clinical signs. Sixteen percent (7/43) of patients were diagnosed with epilepsy, with a median time to diagnosis of 1.34 years (IQR 0.55-2.07) after AVM rupture. One-year epilepsy-free survival was 84% (95% CI 70%-98%) and 2-year epilepsy-free survival was 79% (95% CI 63%-95%) Remote seizures were associated with epilepsy (P < .001), but acute symptomatic seizures were not (P = .16). CONCLUSIONS: EEG-confirmed seizures are uncommon in patients with ICH secondary to AVM rupture; however, when identified, the seizure burden appears to be high. Patients with seizures 30 days after AVM rupture are more likely to develop epilepsy.

5.
J Natl Compr Canc Netw ; 22(7): 438-446, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39236750

RESUMO

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas
6.
Nat Commun ; 15(1): 8350, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333469

RESUMO

A key question in regulatory genomics is whether cis-regulatory elements (CREs) are modular elements that can function anywhere in the genome, or whether they are adapted to certain genomic locations. To distinguish between these possibilities we develop MPIRE (Massively Parallel Integrated Regulatory Elements), a technology for recurrently assaying CREs at thousands of defined locations across the genome in parallel. MPIRE allows us to separate the intrinsic activity of CREs from the effects of their genomic environments. We apply MPIRE to assay three insulator sequences at thousands of genomic locations and find that each insulator functions in locations with distinguishable properties. All three insulators can block enhancers, but each insulator blocks specific enhancers at specific locations. However, only ALOXE3 appears to block heterochromatin silencing. We conclude that insulator function is highly context dependent and that MPIRE is a robust method for revealing the context dependencies of CREs.


Assuntos
Elementos Facilitadores Genéticos , Elementos Isolantes , Elementos Isolantes/genética , Elementos Facilitadores Genéticos/genética , Animais , Genoma/genética , Heterocromatina/genética , Heterocromatina/metabolismo , Genômica/métodos , Camundongos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
7.
Int J Pediatr Otorhinolaryngol ; 186: 112097, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260330

RESUMO

OBJECTIVES: Laryngeal Cleft (LC) is an anatomical defect that can cause swallowing difficulties and subsequent recurrent respiratory symptoms. LC can be treated surgically by performing suture repair or by Injection Laryngoplasty (IL). The indications and efficacy of IL are debated among pediatric otolaryngologists. The aim of this survey study was to review the international perspective on IL for LC. METHODS: An online survey was conducted to assess international opinions on the indications and efficacy of IL for LC patients. An online survey was sent to 250 pediatric otolaryngologists worldwide. The survey included questions on the management of LC, the physicians' experience with IL, and their use of IL. RESULTS: Sixty two (25 %) pediatric otolaryngologists, from 47 medical centers, completed the survey. Of the respondents, 38 (62 %) perform IL. The most reported indication was as a diagnostic tool. For the respondents who did not perform IL, the reasons most reported were that the effect is temporary and that there is a need for a second surgery after IL. CONCLUSION: According to this survey, the perspectives on the use of IL for LC differ among pediatric otolaryngologists, and there is variation in peri-and postoperative standard of care. The respondents' opinions on IL were partly dependent on the intended outcome of its use, i.e., as a permanent treatment or for other indications.

8.
Int J Cancer ; 155(12): 2265-2276, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39175107

RESUMO

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients. This analysis involved a combined approach utilizing histological data and high-dimensional flow cytometry analysis. Our findings indicate that while HGSOC tumors pre-treated with NACT are infiltrated with tumor-reactive CD8+ and CD4+ TIL subsets, only B-TIL and IgA plasma blasts confer prognostic benefit in terms of overall survival. Importantly, the prognostic value of B-TIL and IgA plasma blasts was not restricted to patients treated with NACT, but was also evident in patients treated with PDS. Together, our data point to a critical prognostic role for B-TIL in HGSOC patients independent of T cell status, suggesting that alternative treatment approaches focused on the activation of B cells should be explored for HGSOC.


Assuntos
Linfócitos B , Cistadenocarcinoma Seroso , Linfócitos do Interstício Tumoral , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/imunologia , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Pessoa de Meia-Idade , Idoso , Gradação de Tumores , Procedimentos Cirúrgicos de Citorredução , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante/métodos , Imunoglobulina A
9.
Curr Res Struct Biol ; 8: 100156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131116

RESUMO

Bacteria have evolved elaborate mechanisms to thrive in stressful environments. F-like plasmids in gram-negative bacteria encode for a multi-protein Type IV Secretion System (T4SSF) that is functional for bacterial proliferation and adaptation through the process of conjugation. The periplasmic protein TrbB is believed to have a stabilizing chaperone role in the T4SSF assembly, with TrbB exhibiting disulfide isomerase (DI) activity. In the current report, we demonstrate that the deletion of the disordered N-terminus of TrbBWT, resulting in a truncation construct TrbB37-161, does not affect its catalytic in vitro activity compared to the wild-type protein (p = 0.76). Residues W37-K161, which include the active thioredoxin motif, are sufficient for DI activity. The N-terminus of TrbBWT is disordered as indicated by a structural model of GST-TrbBWT based on ColabFold-AlphaFold2 and Small Angle X-Ray Scattering data and 1H-15N Heteronuclear Single Quantum Correlation (HSQC) spectroscopy of the untagged protein. This disordered region likely contributes to the protein's dynamicity; removal of this region results in a more stable protein based on 1H-15N HSQC and Circular Dichroism Spectroscopies. Lastly, size exclusion chromatography analysis of TrbBWT in the presence of TraW, a T4SSF assembly protein predicted to interact with TrbBWT, does not support the inference of a stable complex forming in vitro. This work advances our understanding of TrbB's structure and function, explores the role of structural disorder in protein dynamics in the context of a T4SSF accessory protein, and highlights the importance of redox-assisted protein folding in the T4SSF.

10.
ACS Synth Biol ; 13(8): 2470-2479, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39096298

RESUMO

Membrane lipid chemistry is remarkably different in archaea compared with bacteria and eukaryotes. In the evolutionary context, this is also termed the lipid divide and is reflected by distinct biosynthetic pathways. Contemporary organisms have almost without exception only one type of membrane lipid. During early membrane evolution, mixed membrane stages likely occurred, and it was hypothesized that the instability of such mixtures was the driving force for the lipid divide. To examine the compatibility between archaeal and bacterial lipids, the bacterium Escherichia coli has been engineered to contain both types of lipids with varying success. Only limited production of archaeal lipid archaetidylethanolamine was achieved. Here, we substantially increased its production in E. coli by overexpression of an archaeal phosphatidylserine synthase needed for ethanolamine headgroup attachment. Furthermore, we introduced a synthetic isoprenoid utilization pathway to increase the supply of isopentenyl-diphosphate and dimethylallyl diphosphate. This improved archaeal lipid production substantially. The archaeal phospholipids also served as a substrate for the E. coli cardiolipin synthase, resulting in archaeal and novel hybrid archaeal/bacterial cardiolipin species not seen in living organisms before. Growth of the E. coli strain with the mixed membrane shows an enhanced sensitivity to the inhibitor of fatty acid biosynthesis, cerulenin, indicating a critical dependence of the engineered E. coli strain on its native phospholipids.


Assuntos
Escherichia coli , Escherichia coli/metabolismo , Escherichia coli/genética , Engenharia Metabólica/métodos , Archaea/metabolismo , Archaea/genética , Lipídeos de Membrana/metabolismo , Lipídeos de Membrana/biossíntese , Terpenos/metabolismo , Compostos Organofosforados/metabolismo , Hemiterpenos/metabolismo , Hemiterpenos/biossíntese , Fosfolipídeos/biossíntese , Fosfolipídeos/metabolismo , Cardiolipinas/metabolismo , Cardiolipinas/biossíntese , CDPdiacilglicerol-Serina O-Fosfatidiltransferase/metabolismo , CDPdiacilglicerol-Serina O-Fosfatidiltransferase/genética , Proteínas de Membrana , Transferases (Outros Grupos de Fosfato Substituídos)
12.
Am J Otolaryngol ; 45(6): 104425, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39096570

RESUMO

PURPOSE: Laryngeal cleft (LC) is an anatomical defect of the larynx, where there is a gap (or cleft) between the arytenoids. Milder types can be treated with injection laryngoplasty (IL), involving injection with a filler, resulting in a decreased depth of the cleft and thereby reducing tracheal penetration or aspiration. The effect, however, is temporary. The aim of this study was to investigate the possible indications and the efficacy of IL for LC. METHODS: Patients who underwent IL for LC between March 2018 and June 2023 were retrospectively evaluated. The following parameters were studied: incidence of LC symptoms and objective swallowing evaluations before and after IL, the duration of possible symptom improvement, complications, and the number of subsequent suture repairs. RESULTS: Eighty-five patients were included. Before IL, 81 (96 %) patients had symptoms of aspiration during feeding, compared to 41 (54 %) patients after IL (p ≤ 0.001). In 42 (49 %) patients, temporary symptom relief occurred, in 22 (26 %) patients symptoms persisted, in 16 (19 %) patients symptoms decreased permanently. Mild complications such as cough and desaturations in the direct postoperative period occurred. CONCLUSION: This study shows a statistically significant decrease in the number of parents/caretakers reporting swallowing symptoms after injection laryngoplasty, and a decrease in the average percentage of parents/caretakers reporting various other symptoms. Based on our results, injection laryngoplasty can be recommended as a diagnostic tool in the treatment of laryngeal cleft. Furthermore, it can be used as bridge therapy (i.e. until patients outgrow their symptoms, or until suture repair).

13.
Physiol Plant ; 176(4): e14463, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39113602

RESUMO

The behavior of many plant enzymes depends on the metals and other ligands to which they are bound. A previous study demonstrated that tobacco Rubisco binds almost equally to magnesium and manganese and rapidly exchanges one metal for the other. The present study characterizes the kinetics of Rubisco and the plastidial malic enzyme when bound to either metal. When Rubisco purified from five C3 species was bound to magnesium rather than manganese, the specificity for CO2 over O2, (Sc/o) increased by 25% and the ratio of the maximum velocities of carboxylation / oxygenation (Vcmax/Vomax) increased by 39%. For the recombinant plastidial malic enzyme, the forward reaction (malate decarboxylation) was 30% slower and the reverse reaction (pyruvate carboxylation) was three times faster when bound to manganese rather than magnesium. Adding 6-phosphoglycerate and NADP+ inhibited carboxylation and oxygenation when Rubisco was bound to magnesium and stimulated oxygenation when it was bound to manganese. Conditions that favored RuBP oxygenation stimulated Rubisco to convert as much as 15% of the total RuBP consumed into pyruvate. These results are consistent with a stromal biochemical pathway in which (1) Rubisco when associated with manganese converts a substantial amount of RuBP into pyruvate, (2) malic enzyme when associated with manganese carboxylates a substantial portion of this pyruvate into malate, and (3) chloroplasts export additional malate into the cytoplasm where it generates NADH for assimilating nitrate into amino acids. Thus, plants may regulate the activities of magnesium and manganese in leaves to balance organic carbon and organic nitrogen as atmospheric CO2 fluctuates.


Assuntos
Cloroplastos , Ribulose-Bifosfato Carboxilase , Cloroplastos/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Ligantes , Dióxido de Carbono/metabolismo , Manganês/metabolismo , Ciclo do Carbono , Oxigênio/metabolismo , Fotossíntese/fisiologia , Magnésio/metabolismo , Metais/metabolismo , Cinética , Carbono/metabolismo , Malatos/metabolismo , Malato Desidrogenase/metabolismo
14.
Nucleic Acids Res ; 52(16): 9481-9500, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39011896

RESUMO

Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC. Epigenome profiling revealed an e1a-induced decrease of H3K27 acetylation and increase of H3K4 monomethylation at derepressed Alus, making them resemble poised enhancers. The enhancer nature of e1a-targeted Alus was confirmed by the enrichment, in their upstream regions, of the EP300/CBP acetyltransferase, EP400 chromatin remodeler and YAP1 and FOS transcription factors. The physical interaction of e1a with EP400 was critical for Alu derepression, which was abrogated upon EP400 ablation. Our data suggest that e1a targets a subset of enhancer Alus whose transcriptional activation, which requires EP400 and is mediated by the e1a-EP400 interaction, may participate in the manipulation of enhancer activity by adenoviruses.


Assuntos
Proteínas E1A de Adenovirus , Elementos Alu , DNA Helicases , Proteínas de Ligação a DNA , Elementos Facilitadores Genéticos , Fator de Transcrição AP-1 , Fatores de Transcrição , Humanos , Elementos Alu/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas E1A de Adenovirus/metabolismo , Proteínas E1A de Adenovirus/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , DNA Helicases/metabolismo , DNA Helicases/genética , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/genética , Montagem e Desmontagem da Cromatina , Proteínas de Sinalização YAP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ativação Transcricional , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Células Cultivadas , Fibroblastos/metabolismo , Histonas/metabolismo , Proteínas Nucleares , Fatores de Transcrição TFIII
15.
Injury ; 55(10): 111734, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39047388

RESUMO

BACKGROUND: Firearms are of special interest in trauma research due to high lethality and criminal value. Strong correlation between guns per capita and fire-arm related deaths has been shown. Most of existing literature regarding gun-shot fatalities are from the U.S. and data for Central Europe is lacking. Thus, the aim of this study was to assess the legal frameworks regarding gun-ownership in Germany (DE), Austria (A) and Switzerland (CH), and to retrospectively analyze data from the TraumaRegister DGU® regarding the epidemiology, injury severity, intention and outcome of gunshot-related deaths in these countries. METHODS: All patients from TR-DGU who sustained a gunshot injury in the time period from 1st January 2009 to 31st December 2019 were considered for analysis. Only cases admitted to level 1 or 2 trauma center in Germany, Switzerland, or Austria were included. Predicted mortality was calculated using the RISC-II. Further, the legal framework for firearm posession were explored. RESULTS: The legal frameworks do not differ significantly between the countries. However, only ex-military men from Switzerland are allowed to keep their automatic (military) weapon at home. We assessed 1312 gunshot fatalities (DE 1,099, A 111, CH 102) of which most were due to suspected suicide (A 72.1 %, CH 64.7 %, and DE 56.6 %, p = 0.003). Act of suspected violent crime or accidental gunshots were rare in all three countries. Amongst all gunshot fatalities, Austria showed the highest mean age (57.6 years), followed by DE (53.4 years) and CH (49.4 years; p < 0.01). Gunshot fatalities amongst all assessed countries due to suspected suicide showed a peak at the age of 60 years and above, whereas suspected violent crime delicts with gunshots were mainly seen in younger age groups. The highest mortality was found in suspected suicide cases, showing a mortality of 82.1 % (predicted 65.2 %) in Switzerland, 75.3 % (predicted 65.8 %) in Austria and 63.7 % (predicted 56.2 %) in Germany. CONCLUSION: Gunshot wounds are still rare in central Europe, but gunshot-related suicide rates are high. Gun ownership laws may have an impact on gunshot wounds due to suspected suicide. Injury patterns differ compared to countries where a high incidence of gun ownership is seen.


Assuntos
Armas de Fogo , Sistema de Registros , Ferimentos por Arma de Fogo , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/mortalidade , Humanos , Suíça/epidemiologia , Alemanha/epidemiologia , Masculino , Áustria/epidemiologia , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Armas de Fogo/legislação & jurisprudência , Armas de Fogo/estatística & dados numéricos , Idoso , Adulto Jovem , Suicídio/estatística & dados numéricos , Adolescente , Propriedade/legislação & jurisprudência , Propriedade/estatística & dados numéricos , Homicídio/estatística & dados numéricos , Homicídio/legislação & jurisprudência , Centros de Traumatologia/estatística & dados numéricos
16.
17.
FASEB J ; 38(11): e23726, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38847773

RESUMO

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of ß-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.


Assuntos
Calcimiméticos , Calcitriol , Osteoblastos , Hormônio Paratireóideo , Animais , Calcitriol/farmacologia , Ratos , Calcimiméticos/farmacologia , Calcimiméticos/uso terapêutico , Hormônio Paratireóideo/farmacologia , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Ratos Wistar , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/metabolismo , Osteogênese/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/complicações , Diferenciação Celular/efeitos dos fármacos , Cálcio/metabolismo
18.
PLoS One ; 19(6): e0304504, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870232

RESUMO

To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm after the virus was inoculated with the biofilm for 5 days at 7°C. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms by conducting plaque assay and qPCR experiments, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81-4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. In addition, we detected an increase in the biofilm biovolume in response to SARS-CoV-2 Delta variant which is also a concern for food safety due to the potential for foodborne pathogens to respond likewise when they come into contact with the virus. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants.


Assuntos
Biofilmes , Embalagem de Alimentos , SARS-CoV-2 , Biofilmes/crescimento & desenvolvimento , SARS-CoV-2/fisiologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Embalagem de Alimentos/métodos , Humanos , COVID-19/microbiologia , COVID-19/virologia , COVID-19/transmissão , Aço Inoxidável , Carne/microbiologia , Carne/virologia
19.
J Clin Invest ; 134(15)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900572

RESUMO

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms (AAs), a devastating vascular disease with a higher prevalence and fatality rate in men than in women. However, the mechanism by which androgen mediates AAs is largely unknown. Here, we found that male, not female, mice developed AAs when exposed to aldosterone and high salt (Aldo-salt). We revealed that androgen and androgen receptors (ARs) were crucial for this sexually dimorphic response to Aldo-salt. We identified programmed cell death protein 1 (PD-1), an immune checkpoint, as a key link between androgen and AAs. Furthermore, we demonstrated that administration of anti-PD-1 Ab and adoptive PD-1-deficient T cell transfer reinstated Aldo-salt-induced AAs in orchiectomized mice and that genetic deletion of PD-1 exacerbated AAs induced by a high-fat diet and angiotensin II (Ang II) in nonorchiectomized mice. Mechanistically, we discovered that the AR bound to the PD-1 promoter to suppress the expression of PD-1 in the spleen. Thus, our study unveils a mechanism by which androgen aggravates AAs by suppressing PD-1 expression in T cells. Moreover, our study suggests that some patients with cancer might benefit from screenings for AAs during immune checkpoint therapy.


Assuntos
Androgênios , Aneurisma Aórtico , Receptor de Morte Celular Programada 1 , Receptores Androgênicos , Animais , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Camundongos , Masculino , Feminino , Androgênios/farmacologia , Androgênios/metabolismo , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Aldosterona/metabolismo , Camundongos Knockout , Humanos , Angiotensina II/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-38729386

RESUMO

BACKGROUND & AIMS: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC with patients with average onset colorectal cancer (AO-CRC) to help define surveillance outcomes in these groups. METHODS: Single-institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps [adenoma/sessile serrated]) were examined. For each group, 3 serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards. RESULTS: A total of 1259 patients with CRC were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared with patients with AO-CRC, patients with EO-CRC had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (hazard ratio, 0.71; 95% confidence interval, 0.52-1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (P = .003), and patients with EO-CRC were found to have less advanced neoplasia compared with their counterparts with AO-CRC (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that, while patients with EO-CRC returned for follow-up surveillance colonoscopy earlier than patients with AO-CRC, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas. CONCLUSIONS: Patients with EO-CRC do not have an increased risk of advanced neoplasia compared with patients with AO-CRC and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA