(1E,3E)-4-acetoxy-1-phenyldimethylsilyl-1,3-butadiene as a surrogate for (1E,3E)-1,4- diacetoxy-1,3-butadiene: a highly efficient synthesis of (+/-)-shikimic acid

The 5-step synthesis of (+/-)-shikimic acid has been achieved in 55% overall yield from (1E,3E)-4-acetoxy-1-phenyldimethylsilyl-1,3-butadiene, starting with its Diels-Alder reaction with 2-(trimethylsilyl)ethyl acrylate and featuring the use of Fleming's one-pot procedure for the conversion of the phenyldimethylsilyl group to the hydroxyl as the salient, pivotal step in the synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28968/1/0000805.pd

siRNA-dependent and -independent post-transcriptional cosuppression of the LTR-retrotransposon MAGGY in the phytopathogenic fungus Magnaporthe oryzae

The LTR-retrotransposon MAGGY was introduced into naive genomes of Magnaporthe oryzae with different genetic backgrounds (wild-type, and MoDcl1 [mdl1] and MoDcl2 [mdl2] dicer mutants). The MoDcl2 mutants deficient in MAGGY siRNA biogenesis generally showed greater MAGGY mRNA accumulation and more rapid increase in MAGGY copy number than did the wild-type and MoDcl1 mutants exhibiting normal MAGGY siRNA accumulation, indicating that RNA silencing functioned as an effective defense against the invading element. Interestingly, however, regardless of genetic background, the rate of MAGGY transposition drastically decreased as its copy number in the genome increased. Notably, in the MoDcl2 mutant, copy-number-dependent MAGGY suppression occurred without a reduction in its mRNA accumulation, and therefore by a silencing mechanism distinct from both transcriptional gene silencing and siRNA-mediated RNA silencing. This might imply that some mechanism possibly similar to post-transcriptional cosuppression of Ty1 retrotransposition in Saccharomyces cerevisiae, which operates regardless of the abundance of target transcript and independent of RNA silencing, would also function in M. oryzae that possesses the RNA silencing machinery

STAT1/3 signaling suppresses axon degeneration and neuronal cell death through regulation of NAD+-biosynthetic and consuming enzymes

Nicotinamide adenine dinucleotide (NAD)+-biosynthetic and consuming enzymes are involved in various intracellular events through the regulation of NAD+ metabolism. Recently, it has become clear that alterations in the expression of NAD+-biosynthetic and consuming enzymes contribute to the axonal stability of neurons. We explored soluble bioactive factor(s) that alter the expression of NAD+-metabolizing enzymes and found that cytokine interferon (IFN)-γ increased the expression of nicotinamide nucleotide adenylyltransferase 2 (NMNAT2), an NAD+-biosynthetic enzyme. IFN-γ activated signal transducers and activators of transcription 1 and 3 (STAT1/3) followed by c-Jun N-terminal kinase (JNK) suppression. As a result, STAT1/3 increased the expression of NMNAT2 at both mRNA and protein levels in a dose- and time-dependent manner and, at the same time, suppressed activation of sterile alpha and Toll/interleukin receptor motif-containing 1 (SARM1), an NAD+-consuming enzyme, and increased intracellular NAD+ levels. We examined the protective effect of STAT1/3 signaling against vincristine-mediated cell injury as a model of chemotherapy-induced peripheral neuropathy (CIPN), in which axonal degeneration is involved in disease progression. We found that IFN-γ-mediated STAT1/3 activation inhibited vincristine-induced downregulation of NMNAT2 and upregulation of SARM1 phosphorylation, resulting in modest suppression of subsequent neurite degradation and cell death. These results indicate that STAT1/3 signaling induces NMNAT2 expression while simultaneously suppressing SARM1 phosphorylation, and that both these actions contribute to suppression of axonal degeneration and cell death

D-dimer trends predict recurrent stroke in patients with cancer-related hypercoagulability

Abstract Introduction: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke. Methods: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 through 2020. The ratio of post-treatment to pre-treatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine–Gray models were used to evaluate the association between post/pre ratio and recurrent stroke. Results: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11–65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61–3.01, p=0.012). Discussion and Conclusion: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke

Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo-resistant. Allogeneic hematopoietic stem cell transplantation is a promising therapy for SS; however, relapse is common. Therapeutic options after relapse have not been established. We managed an SS patient with hematological relapse within one month after transplantation. After discontinuation of immunosuppressants, she achieved complete remission and remained relapse-free. The chimeric analyses of Tcells showed that the full recipient type became complete donor chimera after immunological symptoms. This clinical course suggested that discontinuation of immunosuppressants may result in a graftversus- tumor effect, leading to the eradication of lymphoma cells

Successful intrathecal chemotherapy combined with radiotherapy followed by pomalidomide and low-dose dexamethasone maintenance therapy for a primary plasma cell leukemia patient

Primary plasma cell leukemia (PPCL) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease. Central nervous system (CNS) involvement with PPCL has an extremely poor prognosis. We describe a 46-year-old man with PPCL treated with a combination of lenalidomide, bortezomib, and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation (allo-SCT). Despite achieving a very good partial response, the patient suffered from an isolated CNS relapse 12 months after allo-SCT. He was immediately started on concurrent intrathecal chemotherapy (IT) and cranial irradiation (RT). Subsequently, pomalidomide and low-dose dexamethasone (Pd) were given as maintenance therapy. He has been without CNS recurrence for more than 18 months. Our case suggests that concurrent IT and RT followed by Pd maintenance therapy may be an effective option to control CNS relapse of PPCL after allo-SCT

Ground reaction forces during double limb stances while walking in individuals with unilateral transfemoral amputation

The asymmetrical gait of individuals with unilateral transfemoral amputation has been well documented. However, there is not a wealth of investigation into asymmetries during the double limb stance depending on whether the intact or prosthetic limb is leading. The first aim of this study was to compare ground reaction forces during the double limb stance of individuals with unilateral transfemoral amputation depending on whether their intact (initial double limb stance) or prosthetic (terminal double limb stance) limb was leading. The second aim of this study was to compare the asymmetry ratio of ground reaction forces during the double limb stance between individuals with and without unilateral transfemoral amputation. Thirty individuals, fifteen with unilateral transfemoral amputation and fifteen who were able-bodied, were recruited for this study. Each individual walked on an instrumented treadmill for 30 s at eight different speeds, ranging from 2.0 km/h to 5.5 km/h with .5 km/h increments. Ground reaction force parameters, temporal parameters, and asymmetry ratios of all parameters were computed from the data collected. The appropriate statistical analyses of all data based on normality were conducted to investigate the aims of this study. Significant main effects of speed, double limb stance, and their interactions were found for most parameters (p < .01 or p < .05). Individuals with unilateral transfemoral amputation spent a longer duration in terminal double limb stance than initial double limb stance at all tested speeds. They also experienced significantly higher peak vertical ground reaction force during initial double limb stance compared to terminal double limb stance with increasing walking speed. However, during terminal double limb stance, higher anteroposterior ground reaction force at initial contact was found when compared to initial double limb stance. Significant differences between individuals with unilateral transfemoral amputation and able-bodied individuals were found in asymmetry ratios for peak vertical ground reaction force, anteroposterior ground reaction force, anteroposterior shear, and mediolateral shear at all tested speeds. Asymmetrical loading persists in individuals with unilateral transfemoral amputation during double limb stance. Increasing walking speed increased ground reaction force loading asymmetries, which may make individuals with unilateral transfemoral amputation more susceptible to knee osteoarthritis or other musculoskeletal disorders. Further study is necessary to develop ideal gait strategies for the minimization of gait asymmetry in individuals with unilateral transfemoral amputation

PETREL for Astrophysics and Carbon Business

A multi-purpose 50kg class microsatellite hosting astrophysical mission and earth remote sensing, PETREL , will be launched in 2023. In the night side, PETREL observe the ultra-violet sky with a wide-field telescope covering 50 deg^2 for surveying transient objects related to supernovae, tidal disruption events, and gravitational wave events. Our UV telescope can detect the early phase UV emission from a neutron star merger occurred within 150 Mpc. In addition to the satellite observation, PETREL sends a detection alert including the coordinate and brightness of the UV transient to the ground via the real time communication network within several minutes after detection to conduct follow-up observations with the collaborating ground based observatories over the world. In the day side, PETREL observes the surface of the earth by using the tunable multi-spectral cameras and a ultra-compact hyperspectral camera. Our potential targets are the tropical forests (Green Carbon) and coastal zones (Blue Carbon) in the tropical areas to evaluating the global biological carbon strages. For this purpose PETREL will conduct multiple scale mapping collaborating with drones and small aircraft not only satellite. The obtained data will be used for academical research and for business applications. The technical difficulty of this satellite is that carries out multi-purpose with different requirements, such as astronomical observations which requires a quite high attitude stability and the earth observations requiring a high pointing accuracy, with limited resources. If it is possible, a novel small satellite system or a business style can be realized that can share the payload with academia and industry. PETREL has been adopted as Innovative Satellite Technology Demonstration Program No.3 led by JAXA, and development is underway with the aim of launching in FY2023

ゼンソク チリョウ オ モクテキ トシタ シンキ カゴウブツ ノ ソウセイ ト ゴウセイ

https://library.naist.jp/mylimedio/dllimedio/show.cgi?bookid=100047930&oldid=88865博士 (Doctor)理学 (Science)博第340号甲第340号博士（理学）奈良先端科学技術大学院大