A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase

Background: Examining essential biochemical pathways in Plasmodium falciparum presents serious challenges, as standard molecular techniques such as siRNA cannot be employed in this organism, and generating gene knock-outs of essential proteins requires specialized conditional approaches. In the study of protein kinases, pharmacological inhibition presents a feasible alternative option. However, as in mammalian systems, inhibitors often lack the desired selectivity. Described here is a chemical genetic approach to selectively inhibit Pfnek-2 in P. falciparum, a member of the NIMA-related kinase family that is essential for completion of the sexual development of the parasite. Results: Introduction of a valine to cysteine mutation at position 24 in the glycine rich loop of Pfnek-2 does not affect kinase activity but confers sensitivity to the protein kinase inhibitor 4-(6-ethynyl-9H-purin-2-ylamino) benzene sulfonamide (NCL-00016066). Using a combination of in vitro kinase assays and mass spectrometry, (including phosphoproteomics) the study shows that this compound acts as an irreversible inhibitor to the mutant Pfnek2 likely through a covalent link with the introduced cysteine residue. In particular, this was shown by analysis of total protein mass using mass spectrometry which showed a shift in molecular weight of the mutant kinase in the presence of the inhibitor to be precisely equivalent to the molecular weight of NCL-00016066. A similar molecular weight shift was not observed in the wild type kinase. Importantly, this inhibitor has little activity towards the wild type Pfnek-2 and, therefore, has all the properties of an effective chemical genetic tool that could be employed to determine the cellular targets for Pfnek-2. Conclusions: Allelic replacement of wild-type Pfnek-2 with the mutated kinase will allow for targeted inhibition of Pfnek-2 with NCL-00016066 and hence pave the way for comparative studies aimed at understanding the biological role and transmission-blocking potential of Pfnek-2. © 2016 The Author(s)

The Homeodomain Protein Defective Proventriculus Is Essential for Male Accessory Gland Development to Enhance Fecundity in Drosophila

The Drosophila male accessory gland has functions similar to those of the mammalian prostate gland and the seminal vesicle, and secretes accessory gland proteins into the seminal fluid. Each of the two lobes of the accessory gland is composed of two types of binucleate cell: about 1,000 main cells and 40 secondary cells. A well-known accessory gland protein, sex peptide, is secreted from the main cells and induces female postmating response to increase progeny production, whereas little is known about physiological significance of the secondary cells. The homeodomain transcriptional repressor Defective proventriculus (Dve) is strongly expressed in adult secondary cells, and its mutation resulted in loss of secondary cells, mononucleation of main cells, and reduced size of the accessory gland. dve mutant males had low fecundity despite the presence of sex peptide, and failed to induce the female postmating responses of increased egg laying and reduced sexual receptivity. RNAi-mediated dve knockdown males also had low fecundity with normally binucleate main cells. We provide the first evidence that secondary cells are crucial for male fecundity, and also that Dve activity is required for survival of the secondary cells. These findings provide new insights into a mechanism of fertility/fecundity

A Case of Chronic Infectious Arthritis of the Temporomandibular Joint Associated with Osteomyelitis without Malocclusion

Infectious arthritis of the temporomandibular joint (TMJ) is rare, and previous reports have identified malocclusion resulting from condylar deformity and displacement of the condyle as one of the clinical characteristics of the disease. Here we report the case of a 33-year-old man with chronic infectious arthritis of the TMJ without malocclusion associated with osteomyelitis of the right mandible. Based on radiological findings of more prominent inflammation at the TMJ than in other regions and on the observed efficacy of antibiotic administration, we made a diagnosis of suppurative arthritis of the TMJ. Based on our empirical experience, including the present case, we speculate that refusal to cooperate with medical care may be a factor in the development of infectious arthritis of the TMJ

Value co-creative manufacturing methodology with IoT-based smart factory for mass customisation

Kuik, SS ORCiD: 0000-0002-8179-8688The future of productivity and growth in a highly customized production environment has received much attention by practitioners. This paper presents an innovative methodology of value co-creative manufacturing with Internet of Things (IoT)-based smart factories for mass customized rubber products in a real-time scenario. To implement the proposed system design, a three-layered business oriented model is developed to offer maximum value co-creation for 3D printing technology development by integrating cloud computing and Cyber Physical Systems (CPS) related to computational social science in customized manufacturing and product design. A Japanese case application is presented to demonstrate its usefulness and flexibility for the proposed system design including a computational social scientific approach. © Springer Nature Singapore Pte Ltd. 2017

Value co-creative manufacturing methodology with IoT-based smart factory for mass customisation

The future of productivity and growth in a highly customized production environment has received much attention by practitioners. This paper presents an innovative methodology of value co-creative manufacturing with Internet of Things (IoT)-based smart factories for mass customized rubber products in a real-time scenario. To implement the proposed system design, a three-layered business oriented model is developed to offer maximum value co-creation for 3D printing technology development by integrating cloud computing and Cyber Physical Systems (CPS) related to computational social science in customized manufacturing and product design. A Japanese case application is presented to demonstrate its usefulness and flexibility for the proposed system design including a computational social scientific approach. © Springer Nature Singapore Pte Ltd. 2017

Value co-creative manufacturing with IoT-based smart factory for mass customization

© 2017, Fuji Technology Press. All rights reserved. The future of productivity and growth in highly customized production environments has attracted considerable attention from numerous practitioners. Herein, we present an innovative methodology for value co-creative manufacturing with an Internet of Things (IoT)-based smart factory for mass-customized rubber products in a real-time scenario. For implementing the proposed system, a three-layer business-oriented model is developed to offer the maximum co-creative value in three-dimensional reactive-printing technology development and utilize cloud computing and cyber-physical systems in customized manufacturing and product design. A Japanese case application is examined to demonstrate the usefulness and flexibility of the proposed system

Value Co-Creative Manufacturing with IoT-Based Smart Factory for Mass Customization

© 2017, Fuji Technology Press. All rights reserved. The future of productivity and growth in highly customized production environments has attracted considerable attention from numerous practitioners. Herein, we present an innovative methodology for value co-creative manufacturing with an Internet of Things (IoT)-based smart factory for mass-customized rubber products in a real-time scenario. For implementing the proposed system, a three-layer business-oriented model is developed to offer the maximum co-creative value in three-dimensional reactive-printing technology development and utilize cloud computing and cyber-physical systems in customized manufacturing and product design. A Japanese case application is examined to demonstrate the usefulness and flexibility of the proposed system

SATB 2 suppresses the progression of colorectal cancer cells via inactivation of MEK 5/ERK 5 signaling

Special AT ‐rich sequence binding protein 2 (SATB 2) is an evolutionarily conserved transcription factor that has multiple roles in neuronal development, osteoblast differentiation, and craniofacial patterning. SATB 2 binds to the nuclear matrix attachment region, and regulates the expression of diverse sets of genes by altering chromatin structure. Recent studies have reported that high expression of SATB 2 is associated with favorable prognosis in colorectal and laryngeal cancer; however, it remains uncertain whether SATB 2 has tumor‐suppressive functions in cancer cells. In this study, we examined the effects of SATB 2 expression on the malignant characteristics of colorectal cancer cells. Expression of SATB 2 repressed the proliferation of cancer cells in vitro and in vivo , and also suppressed their migration and invasion. Extracellular signal‐regulated kinase 5 (ERK 5) is a mitogen‐activated protein kinase that is associated with an aggressive phenotype in various types of cancer. SATB 2 expression reduced the activity of ERK 5, and constitutive activation of ERK 5 restored the proliferation, anchorage‐independent growth, migration and invasion of SATB 2‐expressing cells. Our results demonstrate the existence of a novel regulatory mechanism of SATB 2‐mediated tumor suppression via ERK 5 inactivation