Mycobacterium abscessus (MAB) is a species of nontuberculous mycobacteria (NTM) and a major causative pathogen of pulmonary diseases especially in patients with cystic fibrosis. MAB infection is notoriously difficult to treat because of its intrinsic or inducible resistance to most antibiotics. The rough (R) morphotype of MAB, lacking cell surface glycopeptidolipids (GPLs), is associated with more severe and persistent infection than the smooth (S) type; however, the mechanisms underlying the R type’s virulence and the relation with GPLs remain unclear. In this study, we found that R-type MAB is much more proapoptotic than the S type, as a result of GPL-mediated inhibition of macrophage apoptosis. Polar GPLs inhibited an apoptotic response (induced by proapoptotic stimuli) by suppressing ROS production and the cytochrome c release and by preserving mitochondrial transmembrane potential. Furthermore, GPLs were found to be targeted to mitochondria and interacted with cyclophilin D; their acetylation was essential for this interaction. Finally, GPLs inhibited the intracellular growth and bacterial spreading of R-type MAB among macrophages via apoptosis inhibition. These findings suggest that GPLs limit MAB virulence by inhibiting apoptosis and the spread of bacteria and therefore provide a novel insight into the mechanism underlying virulence of MAB.

In this paper, a total of 57 micro and nano scale hybrid manufacturing processes are reviewed. These processes are categorized in terms of process timing and process type. Process timing is one of the most important aspects of manufacturing, and three different process schemes -concurrent, main/assistive (M/S) separate, and main/main (M/M) separate -are considered. The process type is categorized as either geometrically additive or subtractive, and all hybrid processes are categorized into combinations of additive, subtractive, and assistive process. Features and advantages are described for each of these classifications. Machining is found to be the most common process for both micro and nano-scale hybrid manufacturing. Of micro scale hybrid manufacturing schemes, 74.4% use assistive processes as a secondary process because the main purpose of most micro scale hybrid manufacturing is to improve the quality of the process. In nano scale manufacturing, 61.5% of hybrid manufacturing schemes employ assistive processes, since these processes typically focus on the fabrication of parts that are difficult to fabricate using a single, existing process. Based on a summary of published work, future trends in hybrid manufacturing at the micro and nano scale are suggested.

Shape memory alloys (SMAs) are widely utilized as an actuation source in microscale devices, since they have a simple actuation mechanism and high-power density. However, they have limitations in terms of strain range and actuation speed. High-speed microscale SMA actuators are developed having diamond-shaped frame structures with a diameter of 25 µm. These structures allow for a large elongation range compared with bulk SMA materials, with the aid of spring-like behavior under tensile deformation. These actuators are validated in terms of their applicability as an artificial muscle in microscale by investigating their behavior under mechanical deformation and changes in thermal conditions. The shape memory effect is triggered by delivering thermal energy with a laser. The fast heating and cooling phenomenon caused by the scale effect allows high-speed actuation up to 1600 Hz. It is expected that the proposed actuators will contribute to the development of soft robots and biomedical devices.

Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis. Enhanced reactive oxygen species production and JNK activation were essential for MAV2054-mediated apoptosis and MAV2054-induced interleukin-6, tumour necrosis factor, and monocyte chemoattractant protein-1 production. MAV2054 was targeted to the mitochondrial compartment of macrophages treated with MAV2054 and infected with M. avium. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in MAV2054-treated macrophages. Apoptotic response, reactive oxygen species production, and ΔΨm collapse were significantly increased in bone marrow-derived macrophages infected with Mycobacterium smegmatis expressing MAV2054, compared to that in M. smegmatis control. Furthermore, MAV2054 expression suppressed intracellular growth of M. smegmatis and increased the survival rate of M. smegmatis-infected mice. Thus, MAV2054 induces apoptosis via a mitochondrial pathway in macrophages, which may be an innate cellular response to limit intracellular M. avium multiplication.

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