Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity

Living organisms are typically composed of various tissues with microscopic cell-scale stiffness-heterogeneity, in which some cells receive dynamically fluctuating mechanical stimuli from the heterogeneous extracellular milieu during long-term movement. Although intracellular stress dynamics (ISD), which are closely related to the regulation of cell functions such as proliferation and differentiation, can be characteristically modulated in cells migrating on a matrix with stiffness-heterogeneity, it has been unclear how the mode of fluctuation of ISD affects cell functions. In the present study, we demonstrate that mesenchymal stem cells (MSCs) dual-durotaxing (i.e., both forward and reverse durotaxis) on microelastically-patterned gels with stiff triangular domains markedly amplify the fluctuation of ISD, nuclear shape, and the spatial distribution of chromatins, which makes the cells remain far from tensional equilibrium. We provide evidence that amplified chromatin fluctuation in the dual-durotaxing MSCs can cause activation of cellular vigor and maintenance of the stemness.

An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Aberrant inflammation, such as that associated with inflammatory bowel disease (IBD), is fueled by the inordinate activity of RelA/NF-κB factors. As such, the canonical NF-κB module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-κB pathway typically promotes immune organogenesis involving Nfkb2 gene products. Because NF-κB pathways are intertwined, we asked whether noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model of experimental colitis, we established that Nfkb2-mediated regulations escalated the RelA-driven proinflammatory gene response in intestinal epithelial cells, exacerbating the infiltration of inflammatory cells and colon pathologies. Our mechanistic studies clarified that cell-autonomous Nfkb2 signaling supplemented latent NF-κB dimers, leading to a hyperactive canonical RelA response in the inflamed colon. In sum, the regulation of latent NF-κB dimers appears to link noncanonical Nfkb2 signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets.

WASTE CLASSIFICATION ASSESSMENT OF NUCLEAR STEELS FOR FUSION POWER APPLICATIONS

Fusion power is an attractive option for the world’s future energy needs. An important goal for fusion is to avoid the severe radioactive waste issues associated with nuclear fission. However, the neutrons produced in the fusion plasma reaction impinge on the surrounding reactor structure causing nuclear activation. It is hoped that activated material from fusion facilities can be disposed of as low level waste 50-100 years after operation ceases, but recent work suggests this may be difficult to achieve. This work presents inventory simulations for a number of potential fusion steels, for two neutron irradiation conditions typical of the DEMO reactor concept. The results are used to determine if the steels meet low level waste regulations, for a number of different international waste management systems. These results show that steels do not appear able to consistently meet low level waste requirements when exposed to near-plasma neutron fluxes. They have more success when exposed to lower fluxes, but traditional steels will still struggle to meet low level waste requirements in a fusion environment.

Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. At early developmental stages, rnf-145 in the cis-Golgi network inhibits sbp-1 activation to promote the growth of glia, and when animals reach the adult stage, this inhibition is released through an eas-1-dependent shuttling of rnf-145 from the cis-Golgi to the trans-Golgi network to stop glial growth. Furthermore, we identified long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA), as downstream products of the eas-1-rnf-145-sbp-1 pathway that functions to prevent the overgrowth of glia. Together, our findings reveal a novel and potentially conserved mechanism underlying glial size control.

Clinical management of maxillary osteonecrosis associated with antiresorptive medication (MRONJ): Presentation of clinical cases

Antiresorptive drugs: Bisphosphonates (BPs) and Monoclonal Antibodies: Denosumab (DS) are known to suppress osteoclastic activity, affecting the expression of the RANKL (Kappa β Nuclear Activation Receptor), which corresponds to an osteoblastic differentiation factor and which is secreted by said cells, being responsible for inducing reabsorption by osteoclasts. Under certain circumstances, those medications may induce the development of Maxillary Osteonecrosis (MRONJ).The paper is aimed to share our experience of MRONJ treatment using minimally invasive therapies (including washes and antibiotics) that does not expand the necrotic bed volumetrically and provide non-recurrent resolution of the lesion. The patients we described were on long-term therapy either with BPs or DS.Conclusion: Interaction between health professional is essential for MRONJ prevention. The therapeutics consolidated in non-invasive maneuvers, and the manipulation of bone tissue with close follow up allows to avoid spread to deep planes. The pathological process could be successfully treated, and it is not necessary to suspend antiresorptive medications.

An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Aberrant inflammation associated with human ailments, including inflammatory bowel disease (IBD), is typically fuelled by the inordinate activity of RelA/NF-κB transcription factors. As such, the canonical NF-κB module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-κB pathway promotes immune organogenesis involving Nfkb2 gene products. Because NF-κB pathways are intertwined, we asked if noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model, an Nfkb2 function exacerbated gut inflammation by amplifying the epithelial RelA activity induced upon intestinal injury. Our mechanistic studies clarified that cell-autonomous Nfkb2 signaling supplemented latent NF-κB dimers leading to hyperactive canonical RelA response in the inflamed colon. In sum, regulation of latent NF-κB dimers links noncanonical signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets.In briefNoncanonical NF-κB signals in intestinal epithelial cells supplement latent RelA dimers that, in turn, aggravated canonical NF-κB response in the colitogenic gut exacerbating intestinal inflammation.HighlightsHuman IBD involves the frequent engagement of the noncanonical NF-κB pathway.Mice deficient in the noncanonical signal transducer Nfkb2 are resistant to experimental colitis.Noncanonical NF-κB signaling supplements latent RelA NF-κB dimers.Noncanonical NF-κB signaling amplifies canonical NF-κB response to TLR ligands.

Design of a Pixelated Imaging System for Fast Neutron Sources

Imaging detectors that use X-ray radiation and pulsed neutron sources have increased in sophistication in recent years due to the use of solid-state detectors. A key method for neutron detection is the nuclear activation of materials by neutrons. Neutron activation can generate radionuclides whose decay produces secondary particle emission that can be detected without interference from the X-rays and other prompt radiation sources and offers advantages over neutrons detection using scintillators. In this paper, we present the design of an imaging system for fast neutron sources. The imaging system utilizes a microcontroller network that communicates using a modified SPI protocol. This network communicates with an interface unit and passes an image to a personal computer. A computer program has been developed to reconstruct the image.