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1.
Mol Cell ; 79(4): 689-701.e10, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32610038

RESUMO

Meiotic recombination proceeds via binding of RPA, RAD51, and DMC1 to single-stranded DNA (ssDNA) substrates created after formation of programmed DNA double-strand breaks. Here we report high-resolution in vivo maps of RPA and RAD51 in meiosis, mapping their binding locations and lifespans to individual homologous chromosomes using a genetically engineered hybrid mouse. Together with high-resolution microscopy and DMC1 binding maps, we show that DMC1 and RAD51 have distinct spatial localization on ssDNA: DMC1 binds near the break site, and RAD51 binds away from it. We characterize inter-homolog recombination intermediates bound by RPA in vivo, with properties expected for the critical displacement loop (D-loop) intermediates. These data support the hypothesis that DMC1, not RAD51, performs strand exchange in mammalian meiosis. RPA-bound D-loops can be resolved as crossovers or non-crossovers, but crossover-destined D-loops may have longer lifespans. D-loops resemble crossover gene conversions in size, but their extent is similar in both repair pathways.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Recombinação Homóloga , Meiose , Proteínas de Ligação a Fosfato/metabolismo , Rad51 Recombinase/metabolismo , Proteína de Replicação A/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Cromossomos/genética , Cromossomos/metabolismo , Troca Genética , DNA de Cadeia Simples/metabolismo , Genoma , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Proteínas de Ligação a Fosfato/genética , Rad51 Recombinase/genética , Proteína de Replicação A/genética , Testículo
2.
Clin Oral Investig ; 28(7): 399, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922383

RESUMO

OBJECTIVES: The primary objective of this in vitro experiment was an assessment of proliferative capacity, metabolic activity, and potential cellular detriment of human periodontal ligament cells (hPDL) exposed to cigarette smoke (CS), electronic cigarette vapor (eCV), and heated tobacco product aerosol (HTP), or air (control). MATERIALS AND METHODS: Using a CAD/CAM-designed exposition chamber, hPDL were exposed to CS, eCV, HTP, or air (control) based on the Health Canada Intense Smoking Regime. Cell proliferation, metabolic activity, and cellular detriment were assessed at various time points. RESULTS: Compared to the control, hPDL exposed to CS exhibited significantly decreased cell numbers at all time points. HTP exposure led to reduced cell numbers 48 h and 72 h post-exposure, while eCV-exposed cells showed no significant decrease. The metabolic activity of eCV-treated hPDL was slightly reduced at 7 h but recovered at 24 h and 48 h. In contrast, CS-treated cells exhibited significantly decreased metabolic activity at 24 h and 48 h, and HTP-exposed cells showed a significant decrease after 48 h. Flow cytometry indicated both apoptotic and necrotic cell death following CS exposure, with necrotic cell death being more pronounced. CONCLUSIONS: eCV and HTP demonstrated comparatively reduced detrimental effects on hPDL compared to CS. CLINICAL RELEVANCE: The findings suggest that conventional cigarette smoke poses a substantial risk to periodontal health by significantly impairing cell proliferation and metabolic activity. However, alternatives such as eCV and HTP may offer a comparatively reduced risk.


Assuntos
Proliferação de Células , Sistemas Eletrônicos de Liberação de Nicotina , Ligamento Periodontal , Produtos do Tabaco , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Humanos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Produtos do Tabaco/toxicidade , Citometria de Fluxo , Técnicas In Vitro , Fumaça/efeitos adversos , Vapor do Cigarro Eletrônico/toxicidade , Aerossóis , Nicotina/farmacologia , Nicotina/toxicidade , Apoptose/efeitos dos fármacos
3.
Clin Oral Investig ; 28(2): 134, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316644

RESUMO

OBJECTIVES: Oral and maxillofacial surgery (OMFS) has to compete with other specialties for the best candidates. With the upcoming change of generations (Z and Alpha) and the movement toward gender parity of dentistry, understanding changing preferences and misconceptions is essential. MATERIAL AND METHODS: An online survey was conducted by the German-Association-of-Oral-and-Maxillofacial-Surgery (DGMKG) across German dental schools. The survey collected demographic data, academic background, and career aspirations, with a focus on OMFS. The dental student survey results were compared to a survey given to OMFS Specialists. RESULTS: 637 dental students, mainly female (70%), from 30 German universities participated. 27% had defined career aspirations post-graduation, with self-employment and academia being popular choices. 67% were unsure. Specializations leaned towards restorative dentistry (41%), orthodontics (36%), and prosthodontics (31%). While 73% showed interest in surgical practices, 20% were attracted in specializing in OMFS. Of those averse to OMFS, 78% cited long training duration as the deterrent, 12% were put off by perceived unattractive working hours. Other reasons included negative undergraduate experiences, scarcity of part-time positions, and perceived inadequate earnings. CONCLUSION: Accurate data is crucial for career decisions. OMFS societies must proactively share accurate information and guide students. OMFS offers family-friendly hours, and while its training might be longer than dental specialties, it is on par with other surgical professions. CLINICAL RELEVANCE: Dental students consistently regard OMFS as commendable career path. To guarantee sustained OMFS expertise, it is imperative to nurture this interest through dedicated academic mentorship and innovative education, thereby solidifying their professional direction.


Assuntos
Ortodontia , Cirurgia Bucal , Humanos , Feminino , Masculino , Estudantes de Odontologia , Escolha da Profissão , Cirurgia Bucal/educação , Inquéritos e Questionários , Alemanha
4.
Eur Radiol ; 33(10): 7226-7237, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37145149

RESUMO

OBJECTIVES: Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS: Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS: The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION: Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS: • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Disfunção Ventricular Esquerda , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Átrios do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função do Átrio Esquerdo
5.
Clin Oral Investig ; 28(1): 5, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123821

RESUMO

INTRODUCTION: The present study evaluated the biomechanical characteristics of cyanoacrylate-based tissue adhesive (TA) compared to surgical sutures in coronally advanced flap (CAF) procedures using an ex-vivo model. MATERIAL AND METHODS: Thirty-six half-pig mandibles were divided into three groups, n=12 each: (I) CAF fixed with sutures (sling and tag suture technique), (II) CAF fixed with TA, and (III) CAF fixed with sutures and TA. At mandibular premolars, gingival recession defects extending 3 mm apical to the cemento-enamel junction (CEJ) were created. CAF procedures were performed using a split-full-split approach, with coronal advancement of the flap to 1 mm above the marked CEJ and stabilization according to the respective groups I-III. Marginal flap stability against pull-of forces (maximum tensile force) was measured with a universal material testing machine until the CEJ became visible. RESULTS: The comparison between groups I-III demonstrated a significantly increased maximum tensile force for the TA (II) compared to the suture group (I) (p<0.001). A significantly increased maximum tensile force was found for the suture and TA (III) compared to the suture group (I) (p<0.001). There was also a significantly increased maximum tensile force in the suture and TA (III) compared to the TA group (II) (p<0.001). CONCLUSION: The results suggest that cyanoacrylate-based TA can increase marginal flap stability compared to sutures in CAF procedures. CLINICAL RELEVANCE: Cyanoacrylate-based TA can be considered a useful and valuable adjunct to conventional suturing techniques in periodontal plastic surgery, especially in cases where high flap stability is required. The results of this ex-vivo study can only be transferred to the clinical situation with limitations. Clinical long-term follow-up data must be generated.


Assuntos
Retração Gengival , Adesivos Teciduais , Animais , Suínos , Gengiva/cirurgia , Cianoacrilatos , Resultado do Tratamento , Raiz Dentária/cirurgia , Retração Gengival/cirurgia , Suturas
6.
BMC Oral Health ; 23(1): 212, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046245

RESUMO

BACKGROUND: Despite its increasing popularity, to our knowledge the use of social media applications (SM) for residents' training in Oral and Maxillofacial Surgery (OMFS) has not been investigated yet. The aim of this study was to evaluate the use of SM applications by OMFS residents for post-graduate training in Germany. METHODS: For explorative assessment, an online questionnaire containing 27 questions about the current use of SM for resident training was sent to OMFS residents in Germany. RESULTS: Sixty-four colleagues participated to the study. Thirty-four participants (54%) responded to regularly use those platforms mainly for OMFS-related content. YouTube (65%, n = 37), Instagram (48%, n = 27), ResearchGate (25%, n = 14) and WhatsApp (16%, n = 9) were the most popular platforms. (Surgical) videos (97%, n = 59), pictures and graphics (82%, n = 50) were the mainly accessed contents. Forty-four participants (69%) stated that SM substantially contributed to their OMFS training. Dentoalveolar surgery and implantology (66%, n = 35) and aesthetic facial surgery (55%, n = 29) content contributed most to OMFS resident training. Fifty-one participants (80%) recommended an official SM account of the DGMKG. CONCLUSIONS: SM is frequently used by OMFS residents for the consumption of training-related content. There is an imbalance toward dentoalveolar and facial aesthetic surgery regarding the presented content. Academic institutions and societies should complement their educational activities to not miss this emerging educational innovation. Official SM content by academic institutions and societies could contribute to the existing educational activities.


Assuntos
Mídias Sociais , Cirurgia Bucal , Humanos , Cirurgia Bucal/educação , Instituições Acadêmicas , Escolaridade , Inquéritos e Questionários
7.
Medicina (Kaunas) ; 59(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36837455

RESUMO

Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist's ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students' lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease's context and X-ray diagnostics is needed.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Estudantes de Odontologia , Escolaridade , Difosfonatos
8.
Mol Biol Evol ; 38(12): 5555-5562, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34491357

RESUMO

Sterility or subfertility of male hybrid offspring is commonly observed. This phenomenon contributes to reproductive barriers between the parental populations, an early step in the process of speciation. One frequent cause of such infertility is a failure of proper chromosome pairing during male meiosis. In subspecies of the house mouse, the likelihood of successful chromosome synapsis is improved by the binding of the histone methyltransferase PRDM9 to both chromosome homologs at matching positions. Using genetic manipulation, we altered PRDM9 binding to occur more often at matched sites, and find that chromosome pairing defects can be rescued, not only in an intersubspecific cross, but also between distinct species. Using different engineered variants, we demonstrate a quantitative link between the degree of matched homolog binding, chromosome synapsis, and rescue of fertility in hybrids between Mus musculus and Mus spretus. The resulting partial restoration of fertility reveals additional mechanisms at play that act to lock-in the reproductive isolation between these two species.


Assuntos
Infertilidade Masculina , Meiose , Animais , Pareamento Cromossômico , Fertilidade/genética , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Infertilidade Masculina/genética , Masculino , Meiose/genética , Camundongos
9.
Clin Oral Investig ; 26(6): 4499-4507, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35217903

RESUMO

OBJECTIVES: The aim of this study was to analyze the biomechanical characteristics of a novel cyanoacrylate-based tissue adhesive (CTA) for soft-tissue closure of the (non-) tooth-bearing alveolar process and around dental implants. MATERIALS AND METHODS: Halves of porcine mandibles (n = 21) were randomly divided into three experimental intraoral wound closure groups (A-C) with three different mucoperiosteal flap types (F1-3, n = 7 each): F1, crestal incision between the last incisor and the canine with a mesial and distal vestibular relief; F2, crestal double-T-shaped incision and dental implant placement between the canine and the first premolar; and F3, trapezoidal incision on the second premolar. F1-3 were respectively closed using (A) monofil non-resorbable sutures, (B) CTA, and (C) a combination of both. Tensile strength (TS) and elasticity (E) measurements were performed for biomechanical analysis. RESULTS: In F1, CTA showed a significantly reduced TS compared to A (p < 0.001) and C (p < 0.01). In F2, an increased TS of C compared to A (p < 0.01) and B (p < 0.001) was found. Here, E was significantly increased in C compared to B (p < 0.02). In F3, TS was significantly decreased in B compared to A (p < 0.01) and C (p < 0.001). The E in group C was significantly increased compared to B (p < 0.01). CONCLUSIONS: Different biomechanical characteristics between CTA and sutures were found. CTA could be a possible alternative to sutures for intraoral wound closure in special conditions. CLINICAL RELEVANCE: A combination of both, suturing and CTA, could be a promising option in critical soft-tissue wounds requiring high functional stability and elasticity.


Assuntos
Cianoacrilatos , Adesivos Teciduais , Animais , Cianoacrilatos/farmacologia , Técnicas de Sutura , Suturas , Suínos , Adesivos Teciduais/farmacologia , Cicatrização
10.
BMC Neurol ; 21(1): 283, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281522

RESUMO

BACKGROUND: Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH. METHODS: Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated. RESULTS: There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01-1.30) in the entire study population with a lag time of three days. CONCLUSION: Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations.


Assuntos
Pressão Atmosférica , Umidade , Hemorragia Subaracnóidea/epidemiologia , Temperatura , Adulto , Idoso , Estudos Cross-Over , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Medicina (Kaunas) ; 57(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34577888

RESUMO

Oral mucosal melanoma (OMM) represents an extremely rare entity that is associated with a poor prognosis due to late diagnosis and early metastasis. Here, extensive surgical therapy is the therapy of choice. In contrary, for OMM in situ, the respective therapeutical recommendations are lacking. In this case report, treatment modalities of an OMM in situ of the palate, including the maxillary alveolar process, are reported. The tumor relapsed twice despite adequate surgical therapy and reconstruction. Therefore, irradiation was performed as an adjuvant therapy. At a follow-up of two years, the patient was free from recurrences.


Assuntos
Melanoma , Neoplasias Bucais , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , Mucosa Bucal , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia
12.
Arterioscler Thromb Vasc Biol ; 36(6): 1209-19, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27079877

RESUMO

OBJECTIVE: The vascular endothelial growth factor (VEGF) receptor Flk1 is essential for vascular development, but the signaling and transcriptional pathways by which its expression is regulated in endothelial cells remain unclear. Although previous studies have identified 2 Flk1 regulatory enhancers, these are dispensable for Flk1 expression, indicating that additional enhancers contribute to Flk1 regulation in endothelial cells. In the present study, we sought to identify Flk1 enhancers contributing to expression in endothelial cells. APPROACH AND RESULTS: A region of the 10th intron of the Flk1 gene (Flk1in10) was identified as a putative enhancer and tested in mouse and zebrafish transgenic models. This region robustly directed reporter gene expression in arterial endothelial cells. Using a combination of targeted mutagenesis of transcription factor-binding sites and gene silencing of transcription factors, we found that Gata and Ets factors are required for Flk1in10 enhancer activity in all endothelial cells. Furthermore, we showed that activity of the Flk1in10 enhancer is restricted to arteries through repression of gene expression in venous endothelial cells by the Notch pathway transcriptional regulator Rbpj. CONCLUSIONS: This study demonstrates a novel mechanism of arterial-venous identity acquisition, indicates a direct link between the Notch and VEGF signaling pathways, and illustrates how cis-regulatory diversity permits differential expression outcomes from a limited repertoire of transcriptional regulators.


Assuntos
Artérias/metabolismo , Células Endoteliais/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Neovascularização Fisiológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Veias/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Artérias/embriologia , Sítios de Ligação , Elementos Facilitadores Genéticos , Fatores de Transcrição GATA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Genes Reporter , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Íntrons , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , Mutação , Proteínas Proto-Oncogênicas c-ets/metabolismo , Receptores Notch/metabolismo , Fatores de Transcrição SOX/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Veias/embriologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
13.
Proc Natl Acad Sci U S A ; 110(29): 11893-8, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23818617

RESUMO

The mechanisms by which arterial fate is established and maintained are not clearly understood. Although a number of signaling pathways and transcriptional regulators have been implicated in arterio-venous differentiation, none are essential for arterial formation, and the manner in which widely expressed factors may achieve arterial-specific gene regulation is unclear. Using both mouse and zebrafish models, we demonstrate here that arterial specification is regulated combinatorially by Notch signaling and SoxF transcription factors, via direct transcriptional gene activation. Through the identification and characterization of two arterial endothelial cell-specific gene enhancers for the Notch ligand Delta-like ligand 4 (Dll4), we show that arterial Dll4 expression requires the direct binding of both the RBPJ/Notch intracellular domain and SOXF transcription factors. Specific combinatorial, but not individual, loss of SOXF and RBPJ DNA binding ablates all Dll4 enhancer-transgene expression despite the presence of multiple functional ETS binding sites, as does knockdown of sox7;sox18 in combination with loss of Notch signaling. Furthermore, triple knockdown of sox7, sox18 and rbpj also results in ablation of endogenous dll4 expression. Fascinatingly, this combinatorial ablation leads to a loss of arterial markers and the absence of a detectable dorsal aorta, demonstrating the essential roles of SoxF and Notch, together, in the acquisition of arterial identity.


Assuntos
Artérias/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Fatores de Transcrição SOXF/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Artérias/metabolismo , Proteínas de Ligação ao Cálcio , Imunoprecipitação da Cromatina , Clonagem Molecular , Ensaio de Desvio de Mobilidade Eletroforética , Técnicas de Silenciamento de Genes , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Transgênicos , Peixe-Zebra
14.
Proc Biol Sci ; 282(1807): 20142924, 2015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-25904662

RESUMO

Telomeres are protective DNA-protein complexes located at the ends of eukaryotic chromosomes, whose length has been shown to predict life-history parameters in various species. Although this suggests that telomere length is subject to natural selection, its evolutionary dynamics crucially depends on its heritability. Using pedigree data for a population of white-throated dippers (Cinclus cinclus), we test whether and how variation in early-life relative telomere length (RTL, measured as the number of telomeric repeats relative to a control gene using qPCR) is transmitted across generations. We disentangle the relative effects of genes and environment and test for sex-specific patterns of inheritance. There was strong and significant resemblance among offspring sharing the same nest and offspring of the same cohort. Furthermore, although offspring resemble their mother, and there is some indication for an effect of inbreeding, additive genetic variance and heritability are close to zero. We find no evidence for a role of either maternal imprinting or Z-linked inheritance in generating these patterns, suggesting they are due to non-genetic maternal and common environment effects instead. We conclude that in this wild bird population, environmental factors are the main drivers of variation in early-life RTL, which will severely bias estimates of heritability when not modelled explicitly.


Assuntos
Padrões de Herança , Passeriformes/genética , Telômero/genética , Animais , Feminino , Masculino , Passeriformes/fisiologia , Análise de Regressão , Fatores Sexuais
15.
Clin Implant Dent Relat Res ; 26(1): 170-182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37438839

RESUMO

INTRODUCTION: Alveolar ridge augmentation is often required before dental implant placement. In this context, autologous bone grafts are considered the biological gold standard. Still, bone block harvesting is accompanied by some serious potential disadvantages and possible complications, such as pain, bleeding, and nerve irritation. Several studies aimed to compare autologous to allogeneic bone grafts concerning bone quality and implant survival rates; this is the first prospective study analyzing and comparing morbidity-related parameters after alveolar ridge augmentation using autogenous and allogeneic bone blocks from patients' perspective. METHODS: Using a questionnaire, 36 patients were asked to evaluate the surgery as well as the post-operative period concerning pain, stress, sensibility deficits, satisfaction with, and consequences from the surgery as well as the preferred procedure for future alveolar ridge augmentations. RESULTS: No significant differences were shown regarding stress and pain during and after surgery, whereas the rate of nerve irritations was twice as high in the autologous group. The swelling was significantly higher in patients with autologous bone blocks (p = 0.001). Nevertheless, the overall satisfaction of patients of both groups was very high, with over 8/10 points. CONCLUSIONS: The swelling was the main reason for patients' discomfort in both groups and was significantly higher after autologous bone augmentation. Since this side effect seems to be a highly relevant factor for patients' comfort and satisfaction, it needs to be discussed during preoperative consultation to allow shared decision-making considering the anticipated morbidity.


Assuntos
Aumento do Rebordo Alveolar , Transplante de Células-Tronco Hematopoéticas , Humanos , Aumento do Rebordo Alveolar/efeitos adversos , Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endóssea/métodos , Estudos de Coortes , Estudos Prospectivos , Transplante Ósseo/métodos , Dor
16.
Int J Implant Dent ; 10(1): 26, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801622

RESUMO

PURPOSE: Particulate bovine bone substitutes (BS) are commonly used in oral regeneration. However, more literature is needed focusing on comparative analyses among various particulate bovine BS. This study evaluates pre-clinical and clinical data of different particulate bovine BS in oral regeneration. METHODS: A narrative review was conducted by screening the PubMed database Included in the review were pre-clinical and clinical studies until 2024 comparing a minimum of two distinct particulate bovine BS. In addition to examining general data concerning manufacturing and treatment processes, biological safety, physical and chemical characteristics, and graft resorption, particular emphasis was placed on assessing pre-clinical and clinical data related to ridge preservation, sinus floor elevation, peri-implant defects, and various forms of alveolar ridge augmentation utilizing particulate bovine BS. RESULTS: Various treatment temperatures ranging from 300 to 1,250 °C and the employment of chemical cleaning steps were identified for the manufacturing process of particulate bovine BS deemed to possess biosecurity. A notable heterogeneity was observed in the physical and chemical characteristics of particulate bovine BS, with minimal or negligible graft resorption. Variations were evident in particle and pore sizes and the porosity of particulate bovine BS. Pre-clinical assessments noted a marginal inclination towards favorable outcomes for particulate bovine BS subjected to higher treatment temperatures. However, clinical data are insufficient. No distinctions were observed regarding ridge preservation, while slight advantages were noted for high-temperature treated particulate bovine BS in sinus floor elevation. CONCLUSIONS: Subtle variances in both pre-clinical and clinical outcomes were observed in across various particulate bovine BS. Due to inadequate data, numerous considerations related to diverse particulate bovine BS, including peri-implant defects, must be more conclusive. Additional clinical studies are imperative to address these knowledge gaps effectively.


Assuntos
Substitutos Ósseos , Bovinos , Animais , Substitutos Ósseos/uso terapêutico , Humanos , Aumento do Rebordo Alveolar/métodos , Regeneração Óssea/fisiologia
17.
Adv Sci (Weinh) ; 10(28): e2303496, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37562980

RESUMO

Domain insertion engineering is a promising approach to recombine the functions of evolutionarily unrelated proteins. Insertion of light-switchable receptor domains into a selected effector protein, for instance, can yield allosteric effectors with light-dependent activity. However, the parameters that determine domain insertion tolerance and allostery are poorly understood. Here, an unbiased screen is used to systematically assess the domain insertion permissibility of several evolutionary unrelated proteins. Training machine learning models on the resulting data allow to dissect features informative for domain insertion tolerance and revealed sequence conservation statistics as the strongest indicators of suitable insertion sites. Finally, extending the experimental pipeline toward the identification of switchable hybrids results in opto-chemogenetic derivatives of the transcription factor AraC that function as single-protein Boolean logic gates. The study reveals determinants of domain insertion tolerance and yielded multimodally switchable proteins with unique functional properties.


Assuntos
Fatores de Transcrição , Regulação Alostérica
18.
Front Physiol ; 14: 1188802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593237

RESUMO

Introduction: Mechanic power output (MPO) and oxygen consumption (VO2) reflect endurance capacity and are often stated relative to body mass (BM) but less often per skeletal muscle mass (SMM). Rating of perceived exertion (RPE) has previously shown conflicting results between sexes at submaximal intensities. Individual body composition, however, largely differs due to sex and training status. It was the aim of this study to evaluate RPE of untrained and trained individuals of both sexes considering body composition and to estimate whether RPE could be improved as a tool to determine endurance capacity. Methods: The study included 34 untrained adults (age 26.18 ± 6.34 years, 18 women) and 29 endurance trained (age 27.86 ± 5.19, 14 women) who were measured for body composition (InBody 770, InBody Europe B.V., Germany) and tested on a treadmill (Pulsar, H/P/Cosmos, Germany) for aerobic capacity (Metalyzer 3B, Cortex Biophysik GmbH, Germany) in an all-out exercise test applying the Bruce-protocol. VO2, MPO, heart rate (HR), and RPE were obtained at each exercise stage. VO2 and MPO were calculated per BM and SMM. RPE values were correlated with absolute VO2 and MPO, as well as relative to BM, and SMM. HR values and the parameters' standardized values served for comparison to standard procedures. Results: VO2 and MPO were higher in men compared to women and in trained compared to untrained participants. No differences between groups and sexes exist when VO2 and MPO were calculated per BM. When calculated per SMM, VO2 and MPO indicate opposite results already at low intensity stages of exercise test. RPE values had highest correlation with MPO per SMM (R2 = 0.8345) compared to absolute MPO (R2 = 0.7609), or MPO per BM (R2 = 0.8176). Agreement between RPE and MPO per SMM was greater than between RPE and HR (p = 0.008). Conclusion: Although RPE represents a subjective value at first glance, it was shown that RPE constitutes a valuable tool to estimate endurance capacity, which can be further enhanced if individual body composition is considered. Furthermore, MPO and VO2 should be considered relative to SMM. These findings might help to avoid over-exertion, especially among untrained people, by adjusting the training intensity for each subject according to the individual strain evaluated in an exercise test based on individual body composition.

19.
Int J Implant Dent ; 9(1): 20, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37405709

RESUMO

PURPOSE: The macrogeometry of a dental implant plays a decisive role in its primary stability. A larger diameter, a conical shape, and a roughened surface increase the contact area of the implant with the surrounding bone and thus improve primary stability. This is considered the basis for successful implant osseointegration that different factors, such as implant design, can influence. This narrative review aims to critically review macro-geometric features affecting the primary stability of dental implants. METHODS: For this review, a comprehensive literature search and review of relevant studies was conducted based on formulating a research question, searching the literature using keywords and electronic databases such as PubMed, Embase, and Cochrane Library to search for relevant studies. These studies were screened and selected, the study quality was assessed, data were extracted, the results were summarized, and conclusions were drawn. RESULTS: The macrogeometry of a dental implant includes its surface characteristics, size, and shape, all of which play a critical role in its primary stability. At the time of placement, the initial stability of an implant is determined by its contact area with the surrounding bone. Larger diameter and a conical shape of an implant result in a larger contact area and better primary stability. But the linear relationship between implant length and primary stability ends at 12 mm. CONCLUSIONS: Several factors must be considered when choosing the ideal implant geometry, including local factors such as the condition of the bone and soft tissues at the implant site and systemic and patient-specific factors such as osteoporosis, diabetes, or autoimmune diseases. These factors can affect the success of the implant procedure and the long-term stability of an implant. By considering these factors, the surgeon can ensure the greatest possible therapeutic success and minimize the risk of implant failure.


Assuntos
Implantes Dentários , Cirurgiões , Humanos , Implantação Dentária Endóssea/métodos , Osseointegração , Planejamento de Prótese Dentária
20.
Int J Implant Dent ; 8(1): 20, 2022 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429255

RESUMO

PURPOSE: Considering a high prevalence of congenital and especially acquired bleeding disorders, their heterogeneity and the multitude of possible treatments strategies, a review of the scientific data on this topic is needed to implement a treatment guide for healthcare professionals. METHODS: A selective literature review was performed via PubMed for articles describing oral surgery / dental implant procedures in patients with congenital and acquired bleeding disorders. Out of the existing literature, potential treatment algorithms were extrapolated. RESULTS: In order to assess the susceptibility to bleeding, risk stratification can be used for both congenital and acquired coagulation disorders. This risk stratification, together with an appropriate therapeutic pathway, allows for an adequate and individualized therapy for each patient. A central point is the close interdisciplinary cooperation with specialists. In addition to the discontinuation or replacement of existing treatment modalities, local hemostyptic measures are of primary importance. If local measures are not sufficient, systemically administered substances such as desmopressin and blood products have to be used. CONCLUSIONS: Despite the limited evidence, a treatment guide could be developed by means of this narrative review to improve safety for patients and practitioners. Prospective randomized controlled trials are needed to allow the implementation of official evidence-based guidelines.


Assuntos
Transtornos da Coagulação Sanguínea , Implantes Dentários , Transtornos da Coagulação Sanguínea/epidemiologia , Implantes Dentários/efeitos adversos , Hemorragia/terapia , Humanos , Estudos Prospectivos
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