Higher education for sustainable development (HEfSD) is being significantly shaped by the global sustainability agenda. Many higher education institutions, responsible for equipping the next ...generation of sustainability leaders with knowledge and essential skills, proactively try to action the sustainable development goals (SDGs) in HEfSD policy, curriculum and practice through scattered and isolated initiatives. Yet, these attempts are not strategically supported by a governing approach to HEfSD or coordinated effectively to tackle social and environmental sustainability. These predicaments not only widen the gap between HEfSD policy, curriculum and practice but also exacerbate the complexities between human and environmental interactions compromising overall sustainability. However, these efforts represent a potential for actioning the Global Agenda for Sustainable Development. Based on a qualitative research strategy, theory building methodology and various methodological techniques (surveys, policy and literature review, group and individual interviews), this research suggests that the advancement of HEfSD in policy, curriculum and practice depends largely on a better understanding of existing gaps, target areas, commonalities and differences across regional HEfSD agendas. This will hopefully provide higher education institutions and their stakeholders across regions with some conceptual and practical tools to consider strategically how HEfSD can successfully be integrated into policy, curriculum and practice in alignment with SDGs and with the overall mandate of the Global Agenda for Sustainable Development.
Laser ultrasonic waves are promising tools for non-destructive inspection in various industries. To inspect an entire object, the laser beam must scan the complete surface of the object. The incident ...angle of the laser beam will then differ depending on the location on the object that
is irradiated. While oblique incidence of the laser beam will excite ultrasonic waves, there is a possibility that these waves will be different from those excited at normal incidence. For the establishment of reliable inspection techniques, a deeper understanding of laser ultrasonic waves
is required. In this paper, the generation of ultrasonic waves by lasers at oblique incidence is numerically investigated. An integral expression for the temperature distribution that satisfies the thermal conduction is derived and then finite element method (FEM) simulations of the generated
elastic waves are performed. In the case of a small incident angle of the laser beam, the directional dependence of the generated ultrasonic waves is small. However, with a large incident angle, the generated waves exhibit directionality in the wave intensity. Although the incident angle does
not need to be considered in the ordinary use of laser ultrasonic devices, the detectability of defects may be affected when the angle is very large.
Background and purpose: Toll‐like receptor 4 (TLR4) expressed on spinal microglia and astrocytes has been suggested to play an important role in the regulation of pain signalling. The purpose of the ...present work was to examine the links between TLR4, glial activation and spinal release of prostaglandin E2 (PGE2) and tumour necrosis factor (TNF), and the role these factors play in TLR4‐induced tactile allodynia.
Experimental approach: Toll‐like receptor 4 was activated by intrathecal (i.t.) injection of lipopolysaccharide (LPS) and KDO2‐Lipid A (KDO2) to rats. Tactile allodynia was assessed using von Frey filaments and cerebrospinal fluid collected through spinal dialysis and lumbar puncture. PGE2 and TNF levels were measured by mass spectometry and elisa. Minocycline and pentoxifylline (glia inhibitors), etanercept (TNF‐blocker) and ketorolac (COX‐inhibitor) were given i.t. prior to injection of the TLR4‐agonists, in order to determine if these agents alter TLR4‐mediated nociception and the spinal release of PGE2 and TNF.
Key results: Spinal administration of LPS and KDO2 produced a dose‐dependent tactile allodynia, which was attenuated by pentoxifylline, minocycline and etanercept but not ketorolac. Both TLR4 agonists induced the spinal release of PGE2 and TNF. Intrathecal pentoxifylline blunted PGE2 and TNF release, while i.t. minocycline only prevented the spinal release of TNF. The release of PGE2 induced by LPS and KDO2 was attenuated by i.t. administration of ketorolac.
Conclusions and implications: Activation of TLR4 induces tactile allodynia, which is probably mediated by TNF released by activated spinal glia.
BACKGROUNDImmune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients' selection for this therapy is needed. Gene expression profile ...(GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario.METHODSRetrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes.RESULTSThe median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ.CONCLUSIONSThe TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
Abstract Background Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long ...extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients. Methods The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system. Results Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges IR, 754.8–1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9–750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6–688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period. Conclusion Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.
Background and purpose:
Toll‐like receptor 4 (TLR4) expressed on spinal microglia and astrocytes has been suggested to play an important role in the regulation of pain signalling. The purpose of the ...present work was to examine the links between TLR4, glial activation and spinal release of prostaglandin E
2
(PGE
2
) and tumour necrosis factor (TNF), and the role these factors play in TLR4‐induced tactile allodynia.
Experimental approach:
Toll‐like receptor 4 was activated by intrathecal (i.t.) injection of lipopolysaccharide (LPS) and KDO
2
‐Lipid A (KDO
2
) to rats. Tactile allodynia was assessed using von Frey filaments and cerebrospinal fluid collected through spinal dialysis and lumbar puncture. PGE
2
and TNF levels were measured by mass spectometry and
elisa
. Minocycline and pentoxifylline (glia inhibitors), etanercept (TNF‐blocker) and ketorolac (COX‐inhibitor) were given i.t. prior to injection of the TLR4‐agonists, in order to determine if these agents alter TLR4‐mediated nociception and the spinal release of PGE
2
and TNF.
Key results:
Spinal administration of LPS and KDO
2
produced a dose‐dependent tactile allodynia, which was attenuated by pentoxifylline, minocycline and etanercept but not ketorolac. Both TLR4 agonists induced the spinal release of PGE
2
and TNF. Intrathecal pentoxifylline blunted PGE
2
and TNF release, while i.t. minocycline only prevented the spinal release of TNF. The release of PGE
2
induced by LPS and KDO
2
was attenuated by i.t. administration of ketorolac.
Conclusions and implications:
Activation of TLR4 induces tactile allodynia, which is probably mediated by TNF released by activated spinal glia.
The herbicide paraquat is an environmental factor that could be involved in the etiology of Parkinson’s disease. We have previously shown that paraquat penetrates through the blood–brain barrier and ...is taken up by neural cells. In this study, we examined the in vivo toxic mechanism of paraquat to dopamine neurons. GBR-12909, a selective dopamine transporter inhibitor, reduced paraquat uptake into the striatal tissue including dopaminergic terminals. The subchronic treatment with systemic paraquat significantly decreased brain dopamine content in the striatum and slightly in the midbrain and cortex, and was accompanied by the diminished level of its acidic metabolites in rats. When paraquat was administered through a microdialysis probe, a transitory increase in the extracellular levels of glutamate, followed by long-lasting elevations of the extracellular levels of NO
x
− (NO
2
− plus NO
3
−) and dopamine were detected in the striatum of freely moving rats. This dopamine overflow lasted for more than 24 h after the paraquat treatment. Dopamine overflow was inhibited by N
G-nitro-
l-arginine methyl ester, dizocilpine, 6,7-dinitroquinoxaline-2,3-dione and
l-deprenyl. The toxic mechanism of paraquat involves glutamate induced activation of non-NMDA receptors, resulting in activation of NMDA receptor-channels. The influx of Ca
2+ into cells stimulates nitric oxide synthase. Released NO would diffuse to dopaminergic terminals and further induce mitochondrial dysfunction by the formation of peroxynitrite, resulting in continuous and long-lasting dopamine overflow. The constant exposure to low levels of paraquat may lead to the vulnerability of dopaminergic terminals in humans, and might potentiate neurodegeneration caused by the exposure of other substances, such as endogenous dopaminergic toxins.
In nuclear emergencies, it is especially important to carry out a wide range of environmental monitoring and provide the data immediately so as to understand the current distribution of radionuclides ...and investigate countermeasures. Therefore, it is indispensable for a nuclear emergency response to establish a system that supports rapid provision of these data. The authors have been developing the software platform by integrating technologies of environmental monitoring, information processing and network communication, based on the experience of the Fukushima Daiichi Nuclear Accident. It was discovered that the platform is effective in reducing the time needed to publish the monitoring data. Reducing the cost and workload for publishing the monitoring data is also important because monitoring should be continued over a few decades in the case of the Fukushima accident. The authors' platform is expected to help to mitigate the problem, too.
Due to the structural similarity to
N-methyl-4-phenyl pyridinium (MPP
+), paraquat might induce dopaminergic toxicity in the brain. However, its blood–brain barrier (BBB) penetration has not been ...well documented. We studied the manner of BBB penetration and neural cell uptake of paraquat using a brain microdialysis technique with HPLC/UV detection in rats. After subcutaneous administration, paraquat appeared dose-dependently in the dialysate. In contrast, MPP
+ could not penetrate the BBB in either control or paraquat pre-treated rats. These data indicated that the penetration of paraquat into the brain would be mediated by a specific carrier process, not resulting from the destruction of BBB function by paraquat itself or a paraquat radical. To examine whether paraquat was carried across the BBB by a certain amino acid transporter,
l-valine or
l-lysine was pre-administered as a co-substrate. The pre-treatment of
l-valine, which is a high affinity substrate for the neutral amino acid transporter, markedly reduced the BBB penetration of paraquat. When paraquat was administered to the striatum through a microdialysis probe, a significant amount of paraquat was detected in the striatal cells after a sequential 180-min washout with Ringer’s solution. This uptake was significantly inhibited by a low Na
+ condition, but not by treatment with putrescine, a potent uptake inhibitor of paraquat into lung tissue. These findings indicated that paraquat is possibly taken up into the brain by the neutral amino acid transport system, then transported into striatal, possibly neuronal, cells in a Na
+-dependent manner.
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