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1.
Sci Rep ; 14(1): 9495, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664570

RESUMO

The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-ß (TGFß) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization. This known function of TGFß signaling in tendon prompted us to utilize TGFß1 to induce tendon-like structures in 3D tendon constructs. TGFß1 treatment promoted a tendon-like structure in the peripheral layer of the constructs characterized by increased thickness with a gradual decrease in cell density and highly aligned collagen matrix. TGFß1 also enhanced cell proliferation, matrix production, and morphological maturation of cells in the peripheral layer compared to vehicle treatment. TGFß1 treatment also induced early tenogenic differentiation and resulted in sufficient mechanical integrity, allowing biomechanical testing. The current study suggests that this scaffold-free 3D tendon cell culture system could be an in vitro platform to investigate underlying biological mechanisms that regulate tenogenic cell differentiation and matrix organization.


Assuntos
Diferenciação Celular , Proliferação de Células , Tendões , Tenócitos , Fator de Crescimento Transformador beta1 , Animais , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Tendões/citologia , Tendões/metabolismo , Camundongos , Diferenciação Celular/efeitos dos fármacos , Tenócitos/metabolismo , Tenócitos/citologia , Proliferação de Células/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Células Cultivadas , Técnicas de Cultura de Células/métodos , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Engenharia Tecidual/métodos
2.
Bone Res ; 12(1): 17, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472175

RESUMO

While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreERT2; Hif1afl/fl) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreERT2; Hif1afl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.


Assuntos
Ossificação Heterotópica , Osteogênese , Animais , Camundongos , Colágeno/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/genética , Hipóxia/metabolismo , Ossificação Heterotópica/metabolismo , Fatores de Transcrição/metabolismo
3.
Clin Chem Lab Med ; 62(6): 1044-1052, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38366966

RESUMO

INTRODUCTION: Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology. CONTENT: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. SUMMARY: From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52 % female, aged from 29 to 66 years). The methodological quality was moderate in 88 % of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66 % of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59 % in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study). OUTLOOK: Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition.


Assuntos
COVID-19 , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/virologia , COVID-19/diagnóstico , RNA Viral/análise , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Sobreviventes , Fezes/virologia , Fezes/química , Feminino
4.
Arthritis Care Res (Hoboken) ; 76(4): 503-510, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37885103

RESUMO

OBJECTIVE: The purpose of this study was to determine whether clinical, health-related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category. METHODS: This cross-sectional analysis of 823 older adults (mean age 64.6 years, SD 7.8 years) with knee OA and overweight or obesity compared clinical, HRQL, and gait outcomes among obesity classifications (overweight or class I, body mass index [BMI] 27.0-34.9; class II, BMI 35.0-39.9; class III BMI ≥40.0). RESULTS: Patients with class III obesity had worse Western Ontario McMasters Universities Arthritis Index knee pain (0-20) than the overweight or class I (mean 8.6 vs 7.0; difference 1.5; 95% confidence interval [CI] 1.0-2.1; P < 0.0001) and class II (mean 8.6 vs 7.4; difference 1.1; 95% CI 0.6-1.7; P = 0.0002) obesity groups. The Short Form 36 physical HRQL measure was lower in the class III obesity group compared to the overweight or class I (mean 31.0 vs 37.3; difference -6.2; 95% CI -7.8 to -4.7; P < 0.0001) and class II (mean 31.0 vs 35.0; difference -3.9; 95% CI -5.6 to -2.2; P < 0.0001) obesity groups. The class III obesity group had a base of support (cm) during gait that was wider than that for the overweight or class I (mean 14.0 vs 11.6; difference 3.3; 95% CI 2.6-4.0; P < 0.0001) and class II (mean 14.0 vs 11.6; difference 2.4; 95% CI 1.6-3.2; P < 0.0001) obesity groups. CONCLUSION: Among adults with knee OA, those with class III obesity had significantly higher pain levels and worse physical HRQL and gait characteristics compared to adults with overweight or class I or class II obesity.


Assuntos
Osteoartrite do Joelho , Humanos , Idoso , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Sobrepeso , Qualidade de Vida , Estudos Transversais , Obesidade/complicações , Obesidade/diagnóstico , Marcha , Dor , Índice de Massa Corporal
5.
Nat Commun ; 14(1): 2075, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045839

RESUMO

Collagen is a force-bearing, hierarchical structural protein important to all connective tissue. In tendon collagen, high load even below macroscopic failure level creates mechanoradicals by homolytic bond scission, similar to polymers. The location and type of initial rupture sites critically decide on both the mechanical and chemical impact of these micro-ruptures on the tissue, but are yet to be explored. We here use scale-bridging simulations supported by gel electrophoresis and mass spectrometry to determine breakage points in collagen. We find collagen crosslinks, as opposed to the backbone, to harbor the weakest bonds, with one particular bond in trivalent crosslinks as the most dominant rupture site. We identify this bond as sacrificial, rupturing prior to other bonds while maintaining the material's integrity. Also, collagen's weak bonds funnel ruptures such that the potentially harmful mechanoradicals are readily stabilized. Our results suggest this unique failure mode of collagen to be tailored towards combatting an early onset of macroscopic failure and material ageing.


Assuntos
Colágeno , Tecido Conjuntivo , Colágeno/metabolismo , Tecido Conjuntivo/metabolismo , Fenômenos Mecânicos , Polímeros/química , Tendões
6.
Data Brief ; 46: 108787, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36506801

RESUMO

This article describes a dataset of high-resolution visible-spectrum images of safflower (Carthamus tinctorius L.) plants obtained from a LemnaTec Scanalyser automated phenomics platform along with the associated image analysis output and manually acquired biomass data. This series contains 1832 images of 200 diverse safflower genotypes, acquired at the Plant Phenomics Victoria, Horsham, Victoria, Australia. Two Prosilica GT RGB (red-green-blue) cameras were used to generate 6576 × 4384 pixel portable network graphic (PNG) images. Safflower genotypes were either subjected to a salt treatment (250 mM NaCl) or grown as a control (0 mM NaCl) and imaged daily from 15 to 36 days after sowing. Each snapshot consists of four images collected at a point in time; one of which is taken from above (top-view) and the remainder from the side at either 0°, 120° or 240°. The dataset also includes analysis output quantifying traits and describing phenotypes, as well as manually collected biomass and leaf ion content data. The usage of the dataset is already demonstrated in Thoday-Kennedy et al. (2021) [1]. This dataset describes the early growth differences of diverse safflower genotypes and identified genotypes tolerant or susceptible to salinity stress. This dataset provides detailed image analysis parameters for phenotyping a large population of safflower that can be used for the training of image-based trait identification pipelines for a wide range of crop species.

8.
PeerJ ; 10: e12841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35127295

RESUMO

Human usage of coastal water bodies continues to increase and many invertebrates face a broad suite of anthropogenic stressors (e.g., warming, pollution, acidification, fishing pressure). Underwater sound is a stressor that continues to increase in coastal areas, but the potential impact on invertebrates is not well understood. In addition to masking natural sound cues which may be important for behavioral interactions, there is a small but increasing body of scientific literature indicating sublethal physiological stress may occur in invertebrates exposed to high levels of underwater sound, particularly low frequency sounds such as vessel traffic, construction noise, and some types of sonar. Juvenile and sub-adult blue crabs (Callinectes sapidus) and American lobsters (Homarus americanus) were exposed to simulated low-frequency vessel noise (a signal was low-pass filtered below 1 kHz to ensure low-frequency content only) and mid-frequency sonar (a 1-s 1.67 kHz continuous wave pulse followed by a 2.5 to 4.0 kHz 1-s linear frequency modulated chirp) and behavioral response (the animal's activity level) was quantified during and after exposure using EthoVision XT™ from overhead video recordings. Source noise was quantified by particle acceleration and pressure. Physiological response to the insults (stress and recovery) were also quantified by measuring changes in hemolymph heat shock protein (HSP27) and glucose over 7 days post-exposure. In general, physiological indicators returned to baseline levels within approximately 48 h, and no observable difference in mortality between treatment and control animals was detected. However, there was a consistent amplified hemolymph glucose signal present 7 days after exposure for those animals exposed to mid-frequency sound and there were changes to C. sapidus competitive behavior within 24 h of exposure to sound. These results stress the importance of considering the impacts of underwater sound among the suite of stressors facing marine and estuarine invertebrates, and in the discussion of management actions such as protected areas, impact assessments, and marine spatial planning efforts.


Assuntos
Ruído , Som , Animais , Humanos , Ruído/efeitos adversos , Invertebrados , Espectrografia do Som
9.
Matrix Biol ; 105: 53-71, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863915

RESUMO

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix.


Assuntos
Proteoglicanos Pequenos Ricos em Leucina , Neoplasias do Colo do Útero , Animais , Biglicano/genética , Biglicano/metabolismo , Colo do Útero/metabolismo , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Decorina/genética , Decorina/metabolismo , Proteínas da Matriz Extracelular/genética , Feminino , Fibromodulina , Humanos , Lumicana/genética , Camundongos , Gravidez , Proteoglicanos Pequenos Ricos em Leucina/genética
10.
ANZ J Surg ; 92(3): 390-396, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34405511

RESUMO

BACKGROUND: Rectal cancer that grows so close to the anal canal that an adequate distal margin cannot be achieved with a double-stapled anastomosis (DSA) has been managed with abdominoperineal resection. Inter-sphincteric dissection and hand-sewn colo-anal anastomoses (HSCAA) allows anastomosis in some cases where DSA is impossible. There are concerns that HSCAA may lead to complications, local recurrence and poor continence. Our aim was to assess our experience with HSCAA in terms of recurrence, complications, continence and quality of life. METHODS: Consecutive patients at two metropolitan hospitals who underwent an ultra-low anterior resection with hand-sewn colo-anal anastomoses for low rectal cancer during a 10-year period were asked to complete a questionnaire which allowed continence and quality-of-life scores to be calculated. Recurrence and complication rates were obtained from a retrospective medical record review. RESULTS: A total of 26 patients underwent HSCAA. Six patients were not sent a questionnaire (3 deaths, 1 with ileostomy, 1 with ileostomy reversal within 3 months and one who had transferred care to another hospital). Fifteen patients returned questionnaires. Local recurrence occurred in zero cases. Two developed systemic recurrence. Four patients developed anastomotic stricture and three had anastomotic leak. Median Faecal Incontinence Severity Index score was 28 and median FIQoL scores were 3.00, 2.78, 3.86 and 3.00. One patient wished that they had had a permanent stoma rather than anastomosis. CONCLUSION: HSCAA delivered good local control of rectal cancer and high avoidance of permanent stoma. Faecal continence is impaired; however, the results are acceptable to the majority of patients.


Assuntos
Qualidade de Vida , Neoplasias Retais , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Colo/cirurgia , Seguimentos , Humanos , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Matrix Biol Plus ; 12: 100070, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34825162

RESUMO

Tendons and ligaments tend to be pooled into a single category as dense elastic bands of collagenous connective tissue. They do have many similar properties, for example both tissues are flexible cords of fibrous tissue that join bone to either muscle or bone. Tendons and ligaments are both prone to degenerate and rupture with only limited capacity to heal, although tendons tend to heal faster than ligaments. Type I collagen constitutes about 80% of the dry weight of tendons and ligaments and is principally responsible for the core strength of each tissue. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including proline and lysine hydroxylation, hydroxylysine glycosylation and covalent cross-linking. The chemistry, placement and quantity of intramolecular and intermolecular cross-links are believed to be key contributors to the tissue-specific variations in material strength and biological properties of collagens. As tendons and ligaments grow and develop, the collagen cross-links are known to chemically mature, strengthen and change in profile. Accordingly, changes in cross-linking and other post-translational modifications are likely associated with tissue development and degeneration. Using mass spectrometry, we have compared tendon and ligaments from fetal and adult bovine knee joints to investigate changes in collagen post-translational properties. Although hydroxylation levels at the type I collagen helical cross-linking lysine residues were similar in all adult tissues, ligaments had significantly higher levels of glycosylation at these sites compared to tendon. Differences in lysine hydroxylation were also found between the tissues at the telopeptide cross-linking sites. Total collagen cross-linking analysis, including mature trivalent cross-links and immature divalent cross-links, revealed unique cross-linking profiles between tendon and ligament tissues. Tendons were found to have a significantly higher frequency of smaller diameter collagen fibrils compared with ligament, which we suspect is functionally associated with the unique cross-linking profile of each tissue. Understanding the specific molecular characteristics that define and distinguish these specialized tissues will be important to improving the design of orthopedic treatment approaches.

12.
Matrix Biol Plus ; 12: 100077, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34337380

RESUMO

For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the "embryonic" type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer caudal intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the inter-lamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the α1(II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post-translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I-type II collagen transition zone.

13.
Front Plant Sci ; 12: 662498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220887

RESUMO

Salinity is a major contributing factor to the degradation of arable land, and reductions in crop growth and yield. To overcome these limitations, the breeding of crop varieties with improved salt tolerance is needed. This requires effective and high-throughput phenotyping to optimize germplasm enhancement. Safflower (Carthamus tinctorius L.), is an underappreciated but highly versatile oilseed crop, capable of growing in saline and arid environments. To develop an effective and rapid phenotyping protocol to differentiate salt responses in safflower genotypes, experiments were conducted in the automated imaging facility at Plant Phenomics Victoria, Horsham, focussing on digital phenotyping at early vegetative growth. The initial experiment, at 0, 125, 250, and 350 mM sodium chloride (NaCl), showed that 250 mM NaCl was optimum to differentiate salt sensitive and tolerant genotypes. Phenotyping of a diverse set of 200 safflower genotypes using the developed protocol defined four classes of salt tolerance or sensitivity, based on biomass and ion accumulation. Salt tolerance in safflower was dependent on the exclusion of Na+ from shoot tissue and the maintenance of K+ uptake. Salinity response identified in glasshouse experiments showed some consistency with the performance of representatively selected genotypes tested under sodic field conditions. Overall, our results suggest that digital phenotyping can be an effective high-throughput approach in identifying candidate genotypes for salt tolerance in safflower.

14.
Sci Rep ; 11(1): 10868, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035379

RESUMO

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix. Despite the importance of collagen structure and tenocyte function, the biological mechanisms regulating fibrillogenesis and tenocyte maturation are not well understood. Here we examine the function of Reticulocalbin 3 (Rcn3) in collagen fibrillogenesis and tenocyte maturation during postnatal tendon development using a genetic mouse model. Loss of Rcn3 in tendon caused decreased tendon thickness, abnormal tendon cell maturation, and decreased mechanical properties. Interestingly, Rcn3 deficient mice exhibited a smaller collagen fibril distribution and over-hydroxylation in C-telopeptide cross-linking lysine from α1(1) chain. Additionally, the proline 3-hydroxylation sites in type I collagen were also over-hydroxylated in Rcn3 deficient mice. Our data collectively suggest that Rcn3 is a pivotal regulator of collagen fibrillogenesis and tenocyte maturation during postnatal tendon development.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Colágeno/metabolismo , Tendões/crescimento & desenvolvimento , Tendões/metabolismo , Animais , Biomarcadores , Diferenciação Celular , Técnicas de Silenciamento de Genes , Hidrólise , Imuno-Histoquímica , Espectrometria de Massas , Camundongos , Camundongos Knockout , Organogênese/genética , Tendões/embriologia
15.
Elife ; 102021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34036937

RESUMO

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-ß, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice - a phenotype that correlates with the tendon pathology.


Assuntos
Tendão do Calcâneo/patologia , Proteínas da Matriz Extracelular/deficiência , Atividade Motora , Osteogênese Imperfeita/patologia , Osteogênese Imperfeita/fisiopatologia , Ligamento Patelar/patologia , Tendão do Calcâneo/metabolismo , Actinas/metabolismo , Fatores Etários , Animais , Modelos Animais de Doenças , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Genes Recessivos , Predisposição Genética para Doença , Força da Mão , Metaloproteinase 2 da Matriz/metabolismo , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Chaperonas Moleculares/genética , NF-kappa B/metabolismo , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/metabolismo , Ligamento Patelar/metabolismo , Fenótipo , Fosforilação , Resistência Física , Células-Tronco/metabolismo , Células-Tronco/patologia
16.
Nat Commun ; 11(1): 2315, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385229

RESUMO

As established nearly a century ago, mechanoradicals originate from homolytic bond scission in polymers. The existence, nature and biological relevance of mechanoradicals in proteins, instead, are unknown. We here show that mechanical stress on collagen produces radicals and subsequently reactive oxygen species, essential biological signaling molecules. Electron-paramagnetic resonance (EPR) spectroscopy of stretched rat tail tendon, atomistic molecular dynamics simulations and quantum-chemical calculations show that the radicals form by bond scission in the direct vicinity of crosslinks in collagen. Radicals migrate to adjacent clusters of aromatic residues and stabilize on oxidized tyrosyl radicals, giving rise to a distinct EPR spectrum consistent with a stable dihydroxyphenylalanine (DOPA) radical. The protein mechanoradicals, as a yet undiscovered source of oxidative stress, finally convert into hydrogen peroxide. Our study suggests collagen I to have evolved as a radical sponge against mechano-oxidative damage and proposes a mechanism for exercise-induced oxidative stress and redox-mediated pathophysiological processes.


Assuntos
Colágeno/química , Tendões/química , Animais , Materiais Biocompatíveis/química , Biopolímeros/química , Di-Hidroxifenilalanina/química , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/química , Oxirredução , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/química
17.
BMJ Case Rep ; 13(3)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32198227

RESUMO

A 49-year-old man presented to the nearest emergency department profoundly septic with significantly raised inflammatory markers. He had a background of floor of mouth invasive squamous cell carcinoma for which he underwent complex head and neck surgery followed by adjuvant radiotherapy and insertion of a percutaneous gastrostomy tube for feeding. He experienced 3 weeks of retching, cough and malaise. Imaging revealed both an oesophageal perforation and perforated duodenal ulcer, presumed secondary to oesophageal stricturing from his prior surgery and radiotherapy.


Assuntos
Úlcera Duodenal/complicações , Nutrição Enteral/efeitos adversos , Perfuração Esofágica/etiologia , Úlcera Péptica Perfurada/etiologia , Adulto , Diagnóstico Diferencial , Perfuração Esofágica/diagnóstico , Perfuração Esofágica/cirurgia , Gastrostomia , Humanos , Laparotomia , Masculino , Neoplasias Bucais/terapia , Úlcera Péptica Perfurada/diagnóstico , Úlcera Péptica Perfurada/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
18.
Dev Pract ; 30(6): 795-808, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33633435

RESUMO

Using new panel data from the Aid Attitudes Tracker (2013-18), this article draws on a set of 18 actions to map public engagement with global poverty in France, Germany, Great Britain and the United States. It introduces a new engagement segmentation comprised of five distinct groups - the totally disengaged, marginally engaged, informationally engaged, behaviourally engaged, and fully engaged. The data provide evidence of both aggregate and individual-level change in engagement over time but with an important distinction: respondents in less engaged groups are less likely to move out of these groups and tend to stay unengaged. Respondents in more engaged groups are more likely to move in and out of engagement.

20.
Rev. colomb. cienc. pecu ; 32(2): 150-157, abr.-jun. 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1013925

RESUMO

Abstract Background: Paragonimus spp. are trematode parasites that infect human populations worldwide. It is believed that infection rates within Asia reach five to ten percent of the total population. Three of the largest areas of possible infection are Asia, Central and South America as well as Africa, where the total population at risk is estimated to be 293 million people. Humans are infected via ingestion of raw or undercooked decapod crustaceans. Objective: To identify the presence of Paragonimus spp. in crabs from Bogotá, Colombia. Methods: The native crab Neostrengeria macropa and the aquatic invasive crayfish Procambarus clarkii in Bogotá, Colombia, were collected from local markets, pet stores and waterways and dissected to assess the presence of Paragonimus spp. Results: The native crab species, N. macropa (n=29) had an infection prevalence of 17.2%, while the invasive crayfish species, P. clarkii (n=22), had a prevalence of 36.4% combined from both field captured animals and purchased samples. Conclusion: Although the estimated prevalence is lower compared to previous studies in other cities of Colombia, Paragonimus represent a risk to human health. Several environmental factors may contribute to the difference in prevalence including collecting season, rainfall, temperature, altitude and the El Niño Southern Oscillation.


Resumen Antecedentes: Los Paragonimus spp. constituyen un grupo de parásitos tremátodos que infectan a humanos en todo el mundo. Se considera que entre 5 y 10% de la población humana de Asia está infectada. Las áreas con mayor posibilidad de infección son Asia, Centro y Sur América, así como África. Se estima que 293 millones de personas están en riesgo de infección. Los humanos se pueden infectar al consumir crustáceos decápodos crudos. Objetivo: Identificar la presencia de Paragonimus spp. en crustáceos en Bogotá, Colombia. Métodos: Una muestra de cangrejos nativos Neostrengeria macropa y de decápodos invasores Procambarus clarkii fue colectada tanto en mercados locales de Bogotá, como en tiendas de mascotas, ríos, y quebradas. Posteriromente fueron diseccionados para detectar la presencia de Paragonimus spp. Resultados: La prevalencia de la infección en N. macropa (n=29) fue de 17,2%, y en la especie invasora, P. clarkii (n=22), fue de 36,4% (porcentaje combinado de los animales colectados en el campo y los comprados en tiendas). Conclusión: Aunque la prevalencia en este estudio fue más baja que la de otras investigaciones relacionadas, se considera que existe riesgo para la salud humana. Es probable que algunos factores medio ambientales hayan contribuido a la diferencia, incluyendo: temporada de colecta, nivel de lluvias, temperatura, altura, y el fenómeno El Niño.

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