Aims
Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor‐κB (NF‐κB) pathway has been ...documented, knowledge about the genetic alterations leading to the impairment of the NF‐κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL.
Methods
We conducted the systematic sequencing of 21 genes relevant to the NF‐κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation.
Results
The results showed that 68 out of 71 PCNSLs had mutations in the NF‐κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265.
Conclusions
The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B‐cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.
Mutations involving the NF‐κB gene network are common and have a unique profile in primary central nervous system lymphomas.
This paper describes a method for maximum power point tracking (MPPT) control while searching for optimal parameters corresponding to weather conditions at that time. The conventional method has ...problems in that it is impossible to quickly acquire the generation power at the maximum power (MP) point in low solar radiation (irradiation) regions. It is found theoretically and experimentally that the maximum output power and the optimal current, which give this maximum, have a linear relation at a constant temperature. Furthermore, it is also shown that linearity exists between the short-circuit current and the optimal current. MPPT control rules are created based on the findings from solar arrays that can respond at high speeds to variations in irradiation. The proposed MPPT control method sets the output current track on the line that gives the relation between the MP and the optimal current so as to acquire the MP that can be generated at that time by dividing the power and current characteristics into two fields. The method is based on the generated power being a binary function of the output current. Considering the experimental fact that linearity is maintained only at low irradiation below half the maximum irradiation, the proportionality coefficient (voltage coefficient) is compensated for only in regions with more than half the rated optimal current, which correspond to the maximum irradiation. At high irradiation, the voltage coefficient needed to perform the proposed MPPT control is acquired through the hill-climbing method. The effectiveness of the proposed method is verified through experiments under various weather conditions
Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) significantly decrease early in Alzheimer's disease (AD). However, it ...remains unclear whether BDNF/TrkB reductions may be mechanistically involved in the pathogenesis of AD. To address this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout (TrkB(+/-)·5XFAD), and tested the effects of TrkB reduction on AD-like features in this mouse model during an incipient stage that shows only modest amyloid-β (Aβ) pathology and retains normal mnemonic function. TrkB(+/-) reduction exacerbated memory declines in 5XFAD mice at 4-5 months of age as assessed by the hippocampus-dependent spontaneous alternation Y-maze task, while the memory performance was not affected in TrkB(+/-) mice. Meanwhile, TrkB(+/-)·5XFAD mice were normal in nest building, a widely used measure for social behavior, suggesting the memory-specific aggravation of AD-associated behavioral impairments. We found no difference between TrkB(+/-)·5XFAD and 5XFAD control mice in cerebral plaque loads, Aβ concentrations including total Aβ42 and soluble oligomers and β-amyloidogenic processing of amyloid precursor protein. Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate receptor subunits as well as impaired signaling pathways downstream to TrkB such as CREB (cAMP response element-binding protein) and Akt/GSK-3β (glycogen synthase kinase-3β) were observed in TrkB(+/-)·5XFAD mice but not in 5XFAD mice. Among these signaling aberrations, only Akt/GSK-3β dysfunction occurred in TrkB(+/-) mice, while others were synergistic consequences between TrkB reduction and subthreshold levels of Aβ in TrkB(+/-)·5XFAD mice. Collectively, our results indicate that reduced TrkB does not affect β-amyloidosis but exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions in early AD.
Long duration gamma-ray bursts may serve as standard candles to constrain cosmological parameters by probing the Hubble diagram well beyond the range of redshift currently accessible using SNe Ia. ...The standardization of gamma-ray bursts (GRBs) is based on phenomenological relations between two or more parameters found from spectral modeling, one of which is strongly dependent on the cosmological model. The Amati relation links the source-frame energy at which the prompt gamma-ray spectral energy distribution F peaks, and the isotropic-equivalent bolometric energy emitted during the prompt phase. We performed spectral analysis of 26 GRBs with known redshift that have been detected by the Fermi-Large Area Telescope (LAT) during its nine years of operations from 2008 July to 2017 September, thus extending the computation of Eiso to the 100 MeV range. Multiple components are required to fit the spectra of a number of GRBs. We found that the Amati relation is satisfied by the 25 LGRBs, with best-fit parameters similar to previous studies that used data from different satellite experiments, while the only short GRB with known redshift is an outlier. Using the Amati relation, we extend the Hubble diagram to redshift 4.35 and constrain the Hubble constant and dark-energy density in the ΛCDM model, with Fermi-LAT GRBs alone and together with another sample of 94 GRBs and with the latest Supernovae type-Ia data. Our results are consistent with the currently acceptable ranges of those cosmological parameters within errors.
Several reports have been published regarding cost increases attributable to surgical site infections (SSIs) in Europe and the USA. However, such studies have been limited in Japan.
To evaluate the ...economic burden of colorectal SSIs on hospitals in Japan.
This study was undertaken at a Japanese university hospital. Amongst 265 patients who had undergone colorectal surgery in the Department of Coloproctological Surgery between November 2014 and March 2016, 16 patients who developed SSIs and could be allocated a diagnosis procedure combination code were selected as SSI cases. Individual SSI cases were matched to non-SSI cases based on a combination of surgical category, age band, sex, wound class, presence of stoma and risk index. Median length of stay (LOS) and piecework reference cost were compared between SSI episodes and non-SSI episodes.
The median LOS for patients with SSI and without SSI was 25.5 interquartile range (IQR) 21.5–39.3 and 16.5 (IQR 12.5–18.5) days, respectively (P<0.01). The median piecework reference cost for patients with SSI and without SSI was ¥842,155 (IQR ¥716,423–1,388,968) and ¥575,795 (IQR ¥529,638–680,105), respectively (P<0.01).
SSIs led to a significant increase in LOS and economic burden. Although the SSI episodes appear to be more profitable than the non-SSI episodes, the economic profit for SSI episodes was less than that for non-SSI episodes in the observation period, when opportunity costs were taken into account.
Highlights • BACE1+/− mutation significantly reduces Aβ levels irrespective of sex in 5XFAD mice. • BACE1 haploinsufficiency also affects APP processing regardless of sex in 5XFAD mice. • Both Aβ ...oligomers and C99 levels dramatically increase with age in 5XFAD mice. • These β-products of APP are also partially reduced in older BACE1+/− ·5XFAD mice. • BACE1+/− ·5XFAD mice at later age harbor high residual levels of Aβ oligomers and C99.
Development of an Ir-TES for near infrared single photon counting Miura, Y.; Irimatsugawa, T.; Ohno, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2020, Volume:
954
Journal Article
Peer reviewed
A photon-number resolving detector based on an iridium (Ir) transition-edge sensors (TES) for real time dose monitoring was designed and fabricated. The current–voltage relationship of the small ...Ir-TES, with an effective area of 7μm×7μm, was measured and its electrothermal feedback operation was confirmed. This device had a transition temperature of 280 mK, which is higher than that of bulk Ir, because of the proximitisation effect. We also confirm that he signals of infrared photon response were measured.
Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although ...the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5. Calpain overactivation in brains of these mice is accelerated as a result of the marked depletion of the endogenous calpain inhibitor, calpastatin. When levels of this inhibitor are restored in neurons of JNPL3 mice by overexpressing calpastatin, tauopathy is prevented, including calpain-mediated breakdown of cytoskeletal proteins, cdk5 activation, tau hyperphosphorylation, formation of potentially neurotoxic tau fragments by either calpain or caspase-3, and tau oligomerization. Calpastatin overexpression also prevents loss of motor axons, delays disease onset, and extends survival of JNPL3 mice by 3 months to within the range of normal lifespan. Our findings support the therapeutic promise of highly specific calpain inhibition in the treatment of tauopathies and other neurodegenerative states.
Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although the use of titanium oxide ...nanoparticles is regulated, their safety has not been established. Furthermore, the interaction between titanium oxide nanoparticles and various chemical substances and pharmaceuticals is unknown. We co-administered rutile-type titanium oxide nanoparticles (nTR) or anatase-type titanium oxide nanoparticles (nTA) to mice together with paraquat (PQ), cisplatin (CDDP), or anti-5-aminosalicylic acid (5-ASA), and investigated the extent, if any, of liver and kidney injury. As a result, when nTA and nTR were administered alone, no increases were observed in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are indicators of liver damage, or urea nitrogen (BUN), which is an indicator of kidney damage. Next, nTA and nTR were co-administered with PQ, CDDP or 5-ASA. Although no increase in ALT or AST was observed, BUN levels increased significantly and acute kidney injury was induced. The findings suggested that titanium oxide nanoparticles induce acute kidney injury through their interaction with chemicals and drugs.
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