RESUMO
OBJECTIVE: Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). DESIGN: Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 µg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. RESULTS: FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. CONCLUSIONS: Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression.
Assuntos
Osso Esponjoso/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Suporte de Carga , Alendronato/farmacologia , Animais , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Cartilagem Articular/patologia , Modelos Animais de Doenças , Epífises/diagnóstico por imagem , Epífises/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite do Joelho/patologia , Osteófito , Tíbia/efeitos dos fármacos , Tíbia/patologia , Microtomografia por Raio-XRESUMO
BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated (r = 0.315, p = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r = -0.532, p < 0.001) and saliva (r = -0.417, p < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p < 0.05), and were inversely correlated with total lymphocyte (r = -0.43), CD3 (r = -0.55), CD4 (r = -0.60), CD8 (r = -0.41), B (r = -0.482), and NK (r = -0.416) lymphocyte counts (all p < 0.05). INTERPRETATION: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.
Assuntos
COVID-19/virologia , SARS-CoV-2/fisiologia , Saliva/virologia , Carga Viral , Adolescente , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Contagem de Linfócitos , Masculino , Nasofaringe/virologia , SARS-CoV-2/genéticaRESUMO
Protein purification often involves affinity capture of proteins on stationary resin, alternatively proteins are captured on free flowing resin for subsequent separation from bulk fluid. Both methods require labour and time intensive separation of particulate matter from fluid. We present a method where affinity resin is contained within porous-walled containers, supporting clarification, product recovery, and concentration in a single step with minimal hands-on processing time, without significant investments in equipment.
Assuntos
Cromatografia de Afinidade/métodos , Proteínas/isolamento & purificação , Animais , Células CHO , Cromatografia de Afinidade/instrumentação , Cricetinae , Cricetulus , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/isolamento & purificação , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Porosidade , Proteínas/genética , Proteínas/metabolismo , Chá/químicaRESUMO
Inducible expression of the aliphatic amidase operon in Pseudomonas aeruginosa is controlled by an antitermination mechanism which allows production of the full-length transcript only in the presence of small-molecule inducers, such as acetamide. Ligand-regulated antitermination is provided by AmiC, the ligand-sensitive negative regulator, and AmiR, the RNA-binding positive regulator. Under non-inducing or repressing growth conditions, AmiC and AmiR form a complex in which the activity of AmiR is silenced. The crystal structure of the AmiC-AmiR complex identifies AmiR as a new and highly unusual member of the response-regulator family of bacterial signal transduction proteins, regulated by sequestration rather than phosphorylation. Comparison with the structure of free AmiC reveals the subtle mechanism of ligand-induced release of AmiR.