The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA

This research was originally published in Journal of Biological Chemistry. Ahmet Can Berkyurek, Isao Suetake, Kyohei Arita, Kohei Takeshita, Atsushi Nakagawa, Masahiro Shirakawa and Shoji Tajima. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. Journal of Biological Chemistry. 2014; 289, 379-386. © the American Society for Biochemistry and Molecular Biology

Non-coplanar spin structure in a metallic thin film of triangular lattice antiferromagnet CrSe

Tajima Y., Shiogai J., Ueda K., et al. APL Materials, 12, 041112 (2024); licensed under a Creative Commons Attribution (CC BY) license.An antiferromagnetic metal with a two-dimensional triangular network offers a unique playground of intriguing magneto-transport properties and functionalities stemming from the interplay between conducting electrons and intricate magnetic phases. A NiAs-type CrSe is one of the candidates owing to alternate stackings of Cr and Se triangular atomic networks in its crystal structure. While the fabrication of CrSe thin films is indispensable to develop functional devices, studies on its thin-film properties have been limited to date due to the lack of metallic samples. Here, we report on the realization of metallic conductivities of CrSe thin films, which allows us to investigate their intrinsic magneto-transport properties. The metallic sample exhibits a co-occurrence of weak ferromagnetism with perpendicular magnetic anisotropy and antiferromagnetic behavior, indicating the presence of non-coplanar spin structures. In addition, control of the polarity and tilting angle of the non-coplanar spin structure is accomplished by a sign of cooling magnetic fields. The observed non-coplanar spin structure, which can be a source of emergent magnetic field acting on the conducting electrons, highlights the high potential of the triangular lattice antiferromagnet and provides a unique platform for functional thin-film devices composed of NiAs-type derivative Cr chalcogenides and pnictides

Case report: Rehabilitation course in thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly syndrome complicated by cerebral infarction in the left parabolic coronary region

Although thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome was first reported in 2010, its pathogenesis and prognosis are still unknown. Moreover, reports on rehabilitation in patients with TAFRO are limited. In severe cases, dyspnea and muscle weakness could impede improvements in activities of daily living (ADL). However, reports on exercise intensity showed no worsening of TAFRO within the load of 11–13 on the Borg scale. Herein, we describe the rehabilitation and progress in a 61-year-old woman with TAFRO syndrome complicated by cerebral infarction from early onset to discharge. After cerebral infarction onset in the perforating artery, she was admitted to the intensive care unit due to decreased blood pressure and underwent continuous hemodiafiltration. Two weeks following transfer to a general ward, the patient started gait training using a brace due to low blood pressure, respiration, and tachycardia. After initiating gait training, increasing the amount of training was difficult due to a high Borg scale of 15–19, elevated respiratory rate, and worsening tachycardia. Furthermore, there was little improvement in muscle strength on the healthy side after continuous training, owing to long-term steroid administration. On day 100 after transfer, the patient was discharged home with a T-cane gait at a monitored level. The patient had severe hemiplegia due to complications with severe TAFRO syndrome delaying early bed release and gait training; tachycardia; and respiratory distress. Additionally, delayed recovery from muscle weakness on the non-paralyzed side made it difficult for the patient to walk and perform ADLs. Despite these issues, low-frequency rehabilitation was useful. However, low-frequency rehabilitation with gait training, using a Borg scale 15–19 orthosis, did not adversely affect the course of TAFRO syndrome

Association between an 8q24 locus and the risk of colorectal cancer in Japanese

<p>Abstract</p> <p>Background</p> <p>A genome-wide association study (GWAS), which assessed multiple ethnicities, reported an association between single nucleotide polymorphisms in the 8q24 region and colorectal cancer risk. Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited.</p> <p>Methods</p> <p>We conducted a case-control study in 481 patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer controls. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models that considered potential confounders.</p> <p>Results</p> <p>We found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after adjustment for confounders (OR = 1.25). No statistically significant interaction with potential confounding factors was observed.</p> <p>Conclusion</p> <p>The polymorphism rs6983267 showed a significant association with CRC in a Japanese population. Further investigation of the biological mechanism of this association is warranted.</p

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy

A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia

Leukocytes that lack HLA allelic expression are frequently detected in patients with acquired aplastic anemia (AA) who respond to immunosuppressive therapy (IST), although the exact mechanisms underlying the HLA loss and HLA allele repertoire likely to acquire loss-of-function mutations are unknown. We identified a common nonsense mutation at position 19 (c.19C>T, p.R7X) in exon 1 (Exon1mut) of different HLA-A and -B alleles in HLA-lacking granulocytes from AA patients. A droplet digital PCR (ddPCR) assay capable of detecting as few as 0.07% Exon1mut HLA alleles in total DNA revealed the mutation was present in 29% (101/353) of AA patients, with a median allele frequency of 0.42% (range, 0.071% to 21.3%). Exon1mut occurred in only 12 different HLA-A (n=4) and HLA-B (n=8) alleles, including B*40:02 (n=31) and A*02:06 (n=15), which correspond to 4 HLA supertypes (A02, A03, B07, and B44). The percentages of patients who possessed at least one of these 12 HLA alleles were significantly higher in the 353 AA patients (92%,

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations