TAK1 control of cell death Mihaly, S R; Ninomiya-Tsuji, J; Morioka, S
Cell death and differentiation,
11/2014, Letnik:
21, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Programmed cell death, a physiologic process for removing cells, is critically important in normal development and for elimination of damaged cells. Conversely, unattended cell death contributes to a ...variety of human disease pathogenesis. Thus, precise understanding of molecular mechanisms underlying control of cell death is important and relevant to public health. Recent studies emphasize that transforming growth factor-β-activated kinase 1 (TAK1) is a central regulator of cell death and is activated through a diverse set of intra- and extracellular stimuli. The physiologic importance of TAK1 and TAK1-binding proteins in cell survival and death has been demonstrated using a number of genetically engineered mice. These studies uncover an indispensable role of TAK1 and its binding proteins for maintenance of cell viability and tissue homeostasis in a variety of organs. TAK1 is known to control cell viability and inflammation through activating downstream effectors such as NF-κB and mitogen-activated protein kinases (MAPKs). It is also emerging that TAK1 regulates cell survival not solely through NF-κB but also through NF-κB-independent pathways such as oxidative stress and receptor-interacting protein kinase 1 (RIPK1) kinase activity-dependent pathway. Moreover, recent studies have identified TAK1's seemingly paradoxical role to induce programmed necrosis, also referred to as necroptosis. This review summarizes the consequences of TAK1 deficiency in different cell and tissue types from the perspective of cell death and also focuses on the mechanism by which TAK1 complex inhibits or promotes programmed cell death. This review serves to synthesize our current understanding of TAK1 in cell survival and death to identify promising directions for future research and TAK1's potential relevance to human disease pathogenesis.
Post COVID-19 condition of the Omicron variant of SARS-CoV-2 Morioka, S.; Tsuzuki, S.; Suzuki, M. ...
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy,
11/2022, Letnik:
28, Številka:
11
Journal Article
Recenzirano
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To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains.
A single-center cross-sectional study.
Patients who recovered ...from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients’ characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching.
We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively.
The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.
Background
Analysis of the errors in the Raven's Coloured Progressive Matrices (RCPM) has been previously performed for children with intellectual disabilities but has not been investigated for those ...with cerebral palsy (CP). This study aimed to investigate whether the types and positions of errors made by individuals with CP differed from those made by typically developing (TD) controls.
Methods
Forty‐five participants with CP aged 4–18 years and 30 TD children aged 3–9 years underwent RCPM testing. We first compared the RCPM performance and error characteristics between the groups and then examined the association between RCPM and the severity of CP and receptive vocabulary in the CP group.
Results
The results showed that while mean total scores in the two groups were comparable, the types and positions of errors made by individuals with CP differed from those of TD controls. The development of non‐verbal intelligence in children with CP increased with age; when controlling for age, non‐verbal intelligence was significantly correlated with all three functional levels of CP severity and receptive vocabulary.
Conclusions
This study provides valuable insights into the problem‐solving strategies employed by children with CP.
Though nurses have frequent contact with patients, their personal protective equipment (PPE) compliance rate is low, which poses a significant challenge in infection control.
To investigate the ...relative influence of specific factors on PPE compliance.
A sequential two-stage mixed-methods design was applied. In a qualitative study, semi-structured interviews were conducted from May to July 2018. In a quantitative study, a nationwide, cross-sectional survey was conducted from January to March 2019, in which a questionnaire was mailed to 735 nurses in 28 tertiary care hospitals in Japan.
In the quantitative study, 435 (59.2%) analysable responses were obtained. In the linear regression analysis, the lack of the knowledge that ‘standard precaution was the fundamental infection countermeasure applied when patients had signs of infections, and these countermeasures could be terminated if there was no infection found’ was significantly associated with decreased PPE adherence, whereas an antimicrobial-resistant bacteria outbreak or a ward shutdown due to an outbreak and the belief ‘I must never be the cause of spreading infection’ were significantly associated with increased PPE adherence. The β of standard coefficients and t-values of the items were –0.344, –7.784, 0.090, 2.089, 0.088, 2.018, respectively.
This survey systematically identified nursing-associated factors that contribute to PPE compliance. As a practical approach to ensure positive outcomes, we suggest educating nurses by providing adequate knowledge on appropriate PPE use and sharing outbreak or ward shutdown experiences.
Oligodendrocytes are specialized cells that insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify lamin A/C (LMNA/C) as essential for ...transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. These changes are accompanied by altered brain metabolism, lower levels of myelin-related lipids, and altered mitochondrial structure in oligodendrocytes, thereby resulting in myelin thinning and the development of a progressively worsening motor phenotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes.
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•LMNA/C levels increase as oligodendrocyte progenitors differentiate•Lmna deletion in oligodendrocytes impairs their transcriptional signature•Lmna deletion alters brain metabolism, myelin lipids, and mitochondrial structure•Lmna deletion in myelinating glia induces a progressive clinical motor phenotype
Nuclear lamina protein LMNA/C increases as progenitors differentiate. Pruvost et al. identify that it is essential for the transcriptional stability of myelinating oligodendrocytes. Its absence results in aberrant expression of progenitor genes in mature cells, altered lipid metabolism and mitochondrial structure, and onset of a progressively worsening clinical phenotype.
Background and Objective
We developed a quantitative method to measure movement representations of a phantom upper limb using a bimanual circle‐line coordination task (BCT). We investigated whether ...short‐term neurorehabilitation with a virtual reality (VR) system would restore voluntary movement representations and alleviate phantom limb pain (PLP).
Methods
Eight PLP patients were enrolled. In the BCT, they repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb. Drawing circles mentally using the phantom limb led to the emergence of an oval transfiguration of the vertical lines (‘bimanual‐coupling’ effect). We quantitatively measured the degree of this bimanual‐coupling effect as movement representations of the phantom limb before and immediately after short‐term VR neurorehabilitation. This was achieved using an 11‐point numerical rating scale (NRS) for PLP intensity and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). During VR neurorehabilitation, patients wore a head‐mounted display that showed a mirror‐reversed computer graphic image of an intact arm (the virtual phantom limb). By intending to move both limbs simultaneously and similarly, the patients perceived voluntary execution of movement in their phantom limb.
Results
Short‐term VR neurorehabilitation promptly restored voluntary movement representations in the BCT and alleviated PLP (NRS: p = 0.015; 39.1 ± 28.4% relief, SF‐MPQ: p = 0.015; 61.5 ± 48.5% relief). Restoration of phantom limb movement representations and reduced PLP intensity were linearly correlated (p < 0.05).
Conclusions
VR rehabilitation may encourage patient's motivation and multimodal sensorimotor re‐integration of a phantom limb and subsequently have a potent analgesic effect.
Significance
There was no objective evidence that restoring movement representation by neurorehabilitation with virtual reality alleviated phantom limb pain. This study revealed quantitatively that restoring movement representation with virtual reality rehabilitation using a bimanual coordination task correlated with alleviation of phantom limb pain.
Sterol-regulatory element-binding proteins (SREBPs) are key transcription factors regulating cholesterol and fatty acid biosynthesis. SREBP activity is tightly regulated to maintain lipid ...homeostasis, and is modulated upon extracellular stimuli such as growth factors. While the homeostatic SREBP regulation is well studied, stimuli-dependent regulatory mechanisms are still elusive. Here we demonstrate that SREBPs are regulated by a previously uncharacterized mechanism through transforming growth factor-β activated kinase 1 (TAK1), a signaling molecule of inflammation. We found that TAK1 binds to and inhibits mature forms of SREBPs. In an in vivo setting, hepatocyte-specific Tak1 deletion upregulates liver lipid deposition and lipogenic enzymes in the mouse model. Furthermore, hepatic Tak1 deficiency causes steatosis pathologies including elevated blood triglyceride and cholesterol levels, which are established risk factors for the development of hepatocellular carcinoma (HCC) and are indeed correlated with Tak1-deficiency-induced HCC development. Pharmacological inhibition of SREBPs alleviated the steatosis and reduced the expression level of the HCC marker gene in the Tak1-deficient liver. Thus, TAK1 regulation of SREBP critically contributes to the maintenance of liver homeostasis to prevent steatosis, which is a potentially important mechanism to prevent HCC development.
This article presents the results of an academic research project connecting the discipline of ergonomics (and work-related issues) with the theme of sustainability. Despite the stated aim of ...creating value for stakeholders, including employees, companies face difficulties in introducing effective sustainability policies. The research question addressed in this article is the following: How can companies improve their decision-making processes to increase workers' wellbeing using policies integrating issues related to corporate sustainability and ergonomics? Currently, corporate sustainability is focused mainly on the triple bottom line (TBL) concept. In this context, the integration of ergonomics is fragmented and arguably separate from strategic human-resource functions (which have largely been the primary promoter of the internal-social component of corporate sustainability). This research argues that corporate sustainability requires a new step, improving the decision-making process, with the inclusion of more types of rationalities and the recognition of the centrality of workers in the process of creating sustainable action. When corporate sustainability policies focus on worker centrality, they open space for the integration of ergonomics as a pillar of an organization's corporate sustainability strategy. Based on a complex view of work systems, ergonomics can introduce values aligned with sustainability and promote cooperation in organizations. Different stakeholders working at companies can make use of different concepts proposed by ergonomics and other work sciences to support changes in their decision-making processes. In view of broader sustainability objectives, integrating different work-related considerations can help improve performance, including productivity, quality and health.
•Ergonomics and corporate sustainability (CS) have different roots, but converge in the work issue.•Workers and value-based decision paradigm have a central role in promoting and implementing CS.•With strategic support of ergonomics, workers could become key to sustainability.•This research supports the proposal for future ethical stance for ergonomics toward sustainability.•Ergonomists can contribute to CS with their complex view of the work systems.
To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury.
Cross-sectional ...study.
Eleven individuals with spinal cord injury and pain and 10 healthy controls.
Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion.
Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group.
Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.
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