Mechanotransduction of mitochondrial AMPK and its distinct role in flow-induced breast cancer cell migration

The biophysical microenvironment of the tumor site has significant impact on breast cancer progression and metastasis. The importance of altered mechanotransduction in cancerous tissue has been documented, yet its role in the regulation of cellular metabolism and the potential link between cellular energy and cell migration remain poorly understood. In this study, we investigated the role of mechanotransduction in AMP-activated protein kinase (AMPK) activation in breast cancer cells in response to interstitial fluid flow (IFF). Additionally, we explored the involvement of AMPK in breast cancer cell migration. IFF was applied to the 3D cell-matrix construct. The subcellular signaling activity of Src, FAK, and AMPK was visualized in real-time using fluorescent resonance energy transfer (FRET). We observed that breast cancer cells (MDA-MB-231) are more sensitive to IFF than normal epithelial cells (MCF-10A). AMPK was activated at the mitochondria of MDA-MB-231 cells by IFF, but not in other subcellular compartments (i.e., cytosol, plasma membrane, and nucleus). The inhibition of FAK or Src abolished flow-induced AMPK activation in the mitochondria of MDA-MB-231 cells. We also observed that global AMPK activation reduced MDA-MB-231 cell migration. Interestingly, specific AMPK inhibition in the mitochondria reduced cell migration and blocked flow-induced cell migration. Our results suggest the linkage of FAK/Src and mitochondria-specific AMPK in mechanotransduction and the differential role of AMPK in breast cancer cell migration depending on its subcellular compartment-specific activation

Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection.

AimDental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans (S. mutans) can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization.MethodologyControlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides (STAMPs) against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization.ResultsS. mutans colonization was considerably reduced ( +/- 0.4 fold reduction, P=0.01) when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization (5 minutes treatment: 38 +/- 13 fold reduction P=0.01; 16 hours treatment: 96 +/- 28 fold reduction P=0.07).ConclusionS. mutans infection is reduced by the presence of existing biofilms. Thus maintaining a healthy or "normal" biofilm through targeted antimicrobial therapy (such as the STAMPs) could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression

Acute aerobic exercise alters executive control network in preadolescent children

The present study aimed to investigate the effect of acute aerobic exercise on executive function (EF) and executive control network (ECN) in preadolescent children, and further explored the neural basis of acute aerobic exercise on EF in these children. We used a within-subjects design with a counterbalanced order. Nine healthy, right-handed children were scanned with resting-state functional magnetic resonance imaging and performed an EF task both in baseline session and exercise session. The exercise session was consisted of 30 minutes of aerobic exercise on a bicycle ergometer at 60% of their estimated maximum heart rate. Compared with the baseline session, acute aerobic exercise benefitted performance in the EF task, increased the functional connectivity between right dorsolateral prefrontal and left cerebellum, further, the increment of functional connectivity was negatively correlated with the EF' s behavioral performance change. These findings suggest that acute aerobic exercise enhances children's EF, and the neural basis may be related to functional connectivity changes in the ECN elicited by acute aerobic exercise.El objetivo de esta investigación es estudiar la influencia del ejercicio aeróbico agudo en la función ejecutiva (EF) y la red de control ejecutiva (REC) en niños preadolescentes, además explorar la base neutral de estos ejercicios aeróbicos en los niños. Hemos utilizado un diseño de orden equilibrado. Nueve niños diestros saludables fueron escaneados con resonancia magnética funcional y se llevaron a cabo tareas de EF, sesiones de ejercicio y sesiones de medición basal. Comparado con las sesiones de base, la sesión de ejercicio consistió en 30 minutos de ejercicios aeróbicos en bicicleta ergométrica al 60% del ritmo cardiaco máximo estimado. Comparado con la sesión basal, el ejercicio aeróbico agudo benefició el desempeño en la tarea EF, aumentó la conectividad funcional entre el prefrontal dorsolateral derecho y el cerebelo izquierdo, además, el incremento de conectividad funcional se correlacionó negativamente con el cambio en el comportamiento del EF. Los resultados de estos estudios demuestran que el ejercicio aeróbico agudo refuerza, y puede provocar ciertos cambios

N,N′-Bis(2,6-diisopropyl­phen­yl)-3,6-di­methyl-1,2,4,5-tetra­zine-1,4-dicarboxamide

In the title mol­ecule, C30H42N6O2, the amide-substituted N atoms of the tetra­zine ring deviate from the approximate plane of the four other atoms in the ring by 0.457 (3) and 0.463 (3) Å, forming a boat conformation. The two benzene rings form a dihedral angle of 47.69 (9)°. Intra­molecular N—H⋯N and weak C—H⋯O hydrogen bonds are observed

3-(2-Chloro-3,3,3-trifluoro­prop-1-en-1-yl)-2,2-dimethyl-N-[3-(trifluoro­meth­yl)phen­yl]cyclo­propane­carboxamide

In the title mol­ecule, C16H14ClF6NO, the cyclo­propane ring forms a dihedral angle of 70.82 (18)° with the benzene ring. The torsion angles about the ethyl­ene and amide bonds are −2.2 (5) (Cl—C—C—C) and 0.8 (5)° (O—C—N—C). A supra­molecular chain propagated by glide symmetry along [001] and mediated by N—H⋯O hydrogen bonds is observed in the crystal packing