Article
Biochemistry & Molecular Biology
Fiona Jenkinson, Kang Wei Tan, Barbara Schopf, Miguel M. Santos, Philip Zegerman
Summary: In eukaryotes, cyclin-dependent kinase (CDK) inhibits helicase loading factors to ensure the exact duplication of the genome. CDK activates origin firing by phosphorylating Sld2 and Sld3, forming a transient intermediate called the pre-initiation complex (pre-IC). In yeast, the CDK phosphorylations of Sld3 and Sld2 are rapidly turned over by the phosphatases PP2A and PP4 during S phase. This dephosphorylation is important for genome-wide origin firing, pre-IC formation, and maintaining Sld3 dephosphorylation in G1 phase. PP2ARts1 specifically targets Sld3 and its dephosphorylation is critical for replication and cell viability.
Article
Biochemistry & Molecular Biology
Jinfan Wang, Byung-Sik Shin, Carlos Alvarado, Joo-Ran Kim, Jonathan Bohlen, Thomas E. Dever, Joseph D. Puglisi
Summary: Through real-time single-molecule fluorescence spectroscopy, it has been found that the eukaryotic 43S preinitiation complex engages with mRNA through a slow, ATP-dependent process and proceeds to scan rapidly and directionally along the 5' untranslated region (5' UTR). Scanning ribosomes can traverse RNA secondary structures, but hairpin structures near the start codons drive them backward in the 5' direction, requiring rescanning.
Article
Cell Biology
Gea Cereghetti, Caroline Wilson-Zbinden, Vera M. Kissling, Maren Diether, Alexandra Arm, Haneul Yoo, Ilaria Piazza, Shady Saad, Paola Picotti, D. Allan Drummond, Uwe Sauer, Reinhard Dechant, Matthias Peter
Summary: The glycolytic metabolite fructose-1,6-bisphosphate is able to initiate the disassembly of inactive amyloids formed by Cdc19 during stress, leading to the restoration of ATP production and disassembly of stress granules (SGs) in yeast cells. This mechanism directly links cellular metabolism with SG dynamics, and plays a critical role in stress recovery by promoting Cdc19 re-solubilization and enhancing ATP production.
NATURE CELL BIOLOGY
(2021)
Article
Biology
Mark C. Johnson, Geylani Can, Miguel Monteiro Santos, Diana Alexander, Philip Zegerman
Summary: This study reveals that Rad53 phosphorylates the same substrates throughout the cell cycle, not just in S-phase, suggesting its roles beyond S-phase. By inhibiting 51d3 and Dbf4, Rad53 limits re-replication in G2/M, preventing gene amplification, and inhibiting these substrates in G1 prevents premature initiation at the G1/S transition. This redefinition of the 'S-phase checkpoint' has implications for understanding checkpoint function in cancers without proper cell cycle controls.
Article
Multidisciplinary Sciences
Ebelechukwu C. Nwokoye, Eiman AlNaseem, Robert A. Crawford, Lydia M. Castelli, Martin D. Jennings, Christopher J. Kershaw, Graham D. Pavitt
Summary: By interacting with eIF4E and ribosomes, Caf20 influences mRNA selection and protein synthesis, with the exact mechanism remaining unclear.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ishita Joshi, Jie Peng, Gina Alvino, Elizabeth Kwan, Wenyi Feng
Summary: This study compared replication origin activation in two yeast strains under hydroxyurea treatment, revealing the roles of S-phase checkpoint control, DNA sequence polymorphisms, and origin-transcription unit positioning. Rad53 protein plays a significant role in activation of origins, particularly in checkpoint-proficient cells.
Article
Biochemistry & Molecular Biology
Simone Pelliciari, Mei-Jing Dong, Feng Gao, Heath Murray
Summary: Genome replication is essential for cell proliferation, and a basal mechanism for opening bacterial chromosome origins has been proposed recently. Core elements of this mechanism are predicted to be present in the majority of bacterial chromosome origins, indicating functional conservation and a potential ancestral system for opening bacterial chromosome origins.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Marcus G. Bage, Rajaei Almohammed, Victoria H. Cowling, Andrei Pisliakov
Summary: Recruitment of the mRNA capping enzyme to the site of transcription is crucial for the formation of the 5' mRNA cap, ensuring efficient transcription, splicing, polyadenylation, nuclear export, and translation of mRNA in eukaryotic cells. Molecular dynamics simulations and enhanced sampling techniques were used to characterize the human CE-CTD interface, revealing novel CTD interaction sites on the human CE GTase surface and proposing a mechanism for allosteric activation. Validation through binding and activity assays confirmed the essential role of the CDS2 site in CE GTase activity stimulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Michael Reidy, Kevin Garzillo, Daniel C. Masison
Summary: Hsp90 is an essential eukaryotic chaperone that regulates protein activity. The Hsp82-E33A mutant, which binds ATP but does not hydrolyze it, supports viability of S. cerevisiae and other eukaryotic species, suggesting that ATP hydrolysis is not necessary for Hsp90 function. The exchange of ATP for ADP is critical for Hsp90 function, with ATP hydrolysis providing an important control point regulated by co-chaperones.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alexandr A. Tomashevsky, Valery V. Petrov
Summary: Both ATP and inorganic polyphosphates are involved in yeast energy homeostasis, with the PMA1 H+-ATPase playing a key role. The structure and phosphorylation of the enzyme affect its function and its relationship with PolyP metabolism. Substitutions of specific residues in different domains of the enzyme have varied effects on PolyP content and distribution, depending on the type of substitution and its impact on ATPase activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biotechnology & Applied Microbiology
Anne Usvalampi, He Li, Alexander D. Frey
Summary: This study established a fully enzymatic route for synthesizing glucose 6-phosphate from cellulose, achieving a high conversion rate under optimized conditions. However, in the reaction involving cellulase release of glucose from cellulose, a high conversion rate was attained but at the cost of lower yield of glucose 6-phosphate.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Calla B. Shubin, Rini Mayangsari, Ariel D. Swett, Carol W. Greider
Summary: In budding yeast, Rif1 negatively regulates telomere length through a region with HEAT repeats that mediate telomere length regulation, separate from its proposed DNA binding function. Conserved amino acids from position 436 to 577 play a crucial role in telomere length regulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Max A. B. Haase, Guojon Olafsson, Rachel L. Flores, Emmanuel Boakye-Ansah, Alex Zelter, Miles Sasha Dickinson, Luciana Lazar-Stefanita, David M. Truong, Charles L. Asbury, Trisha N. Davis, Jef D. Boeke
Summary: Forcing budding yeast to use human histones to chromatinize their DNA comes with a sudden fitness cost. Previous research suggested chromosomal aneuploidy and missense mutations as two potential adaptation modes to histone humanization. However, we found that aneuploidy in histone-humanized yeasts is specific to certain chromosomes with defined centromeric evolutionary origins, but these aneuploidies are not adaptive. Instead, a set of missense mutations in outer kinetochore proteins are driving the adaptation to human histones.
Article
Biochemistry & Molecular Biology
Titi Rindi Antika, Kun Rohmatan Nazilah, Yi-Hsueh Lee, Ya-Ting Lo, Chung-Shu Yeh, Fu-Lung Yeh, Tien-Hsien Chang, Tzu-Ling Wang, Chien-Chia Wang
Summary: In this study, it was found that mature native human tRNA(m)(His) contains only G-1. ATP is required for HsThg1 to catalyze the addition of G-1 to tRNA(m)(His). HsThg1 possesses a tRNA-inducible GTPase activity, which can inhibit the incorporation of multiple GTPs into tRNA(m)(His).
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Rafael Jimenez-Lorenzo, Vincent Farines, Jean-Marie Sablayrolles, Carole Camarasa, Audrey Bloem
Summary: Volatile sulfur compounds (VSCs) in wine, which cause unpleasant aromas and reduce quality, are formed and evolved during fermentation and aging through both yeast metabolism and chemical reactions.
FERMENTATION-BASEL
(2022)
Article
Surgery
Mitsuyoshi Tei, Yozo Suzuki, Masahisa Ohtsuka, Tsunekazu Mizushima, Hiroki Akamatsu
Summary: Single-incision laparoscopic complete mesocolic excision with central vascular ligation is safe and feasible for descending colon cancer, according to this study. Standardization of the surgical procedures is crucial.
Article
Gastroenterology & Hepatology
Mitsuyoshi Tei, Yozo Suzuki, Masahisa Ohtsuka, Kazuya Iwamoto, Atsushi Naito, Mitsunobu Imasato, Tsunekazu Mizushima, Hiroki Akamatsu
Summary: This study retrospectively analyzed the clinical outcomes of single incision laparoscopic surgery (SILS) for colorectal cancer (CRC) performed by novice surgeons compared with experienced surgeons. The results showed that SILS for CRC could be safely performed by novice surgeons under the guidance of well-experienced surgeons, and satisfactory oncological outcomes were achieved.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Gastroenterology & Hepatology
Chu Matsuda, Toshihiro Kudo, Yoshihiro Morimoto, Yoshinori Kagawa, Mitsuyoshi Tei, Yoshihito Ide, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Ichiro Takemasa, Taroh Satoh, Tsunekazu Mizushima, Kohei Murata, Yuichiro Doki, Hidetoshi Eguchi
Summary: The purpose of this study was to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan as neoadjuvant chemotherapy in patients with locally advanced rectal cancer. The results showed that XELOXIRI neoadjuvant chemotherapy is feasible and efficacious for patients with LARC, although it did not achieve the expected complete response rate, the local recurrence rate, 3-year disease-free survival rate, and safety measures met current standards.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Oncology
Yukihiro Yoshikawa, Mitsuko Fukunaga, Junichi Takahashi, Dai Shimizu, Takaaki Masuda, Tsunekazu Mizushima, Kazutaka Yamada, Masaki Mori, Hidetoshi Eguchi, Yuichiro Doki, Takahiro Ochiya, Koshi Mimori
Summary: This study identified the ideal combination of miRNAs for predicting colorectal cancer recurrence. These miRNAs showed better predictive ability compared to conventional tumor markers.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Satomi Furukawa, Tsunekazu Mizushima, Ryo Nakaya, Mari Shibata, Takayoshi Yamaguchi, Kenji Watanabe, Kitaro Futami
Summary: This study evaluated the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn's disease. The results showed that the proportion of patients achieving combined remission at 24 weeks and 52 weeks was 59.1% and 68.2% respectively, and no new safety issues were identified.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Surgery
Shiro Nakamura, Motoshi Wada, Tsunekazu Mizushima, Akira Sugita, Yuko Tazuke, Hiroki Ohge, Eri Udagawa, Ryohsuke Ken Suzuki, MinJung Yoon, Andrew Grimm, Szu-Ta Chen, Hiroki Ikeuchi
Summary: Treatment with teduglutide in Japanese adults with SBS-IF can lead to clinically meaningful reductions in parenteral support requirements, and is safe for short- and long-term use.
Article
Gastroenterology & Hepatology
Takehiro Noda, Hidekazu Takahashi, Mitsuyoshi Tei, Naohiro Nishida, Taishi Hata, Yutaka Takeda, Masayuki Ohue, Hiroshi Wada, Tsunekazu Mizushima, Tadafumi Asaoka, Mamoru Uemura, Shogo Kobayashi, Kohei Murata, Taroh Satoh, Yuichiro Doki, Hidetoshi Eguchi
Summary: This study investigated the clinical outcomes of neoadjuvant chemotherapy for resectable colorectal liver metastasis (CRLM) according to patient risk status. The results showed that patients in the intermediate-risk group who received neoadjuvant chemotherapy had significantly better recurrence-free survival, but overall survival was not improved.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Gastroenterology & Hepatology
Masaaki Miyo, Tsunekazu Mizushima, Junichi Nishimura, Taishi Hata, Mitsuyoshi Tei, Yuichiro Miyake, Yoshinori Kagawa, Shingo Noura, Masakazu Ikenaga, Katsuki Danno, Atsuhiro Ogawa, Yoshinao Chinen, Tsuyoshi Hata, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Hirofumi Yamamoto, Kohei Murata, Yuichiro Doki, Hidetoshi Eguchi
Summary: This multicenter retrospective study examined the impact of the COVID-19 pandemic on colorectal cancer treatment in Japan. The study found that the pandemic resulted in a reduction in the number of surgeries and colonoscopies performed for colorectal cancer and hindered the detection of early-stage cancers. The impact varied depending on the size of the hospital.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Gastroenterology & Hepatology
Masakatsu Paku, Mamoru Uemura, Masatoshi Kitakaze, Norikatsu Miyoshi, Hidekazu Takahashi, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi
Summary: This study aimed to evaluate the relationship between perioperative serum CEA/carbohydrate antigen 19-9 levels and prognosis in locally recurrent rectal cancer. The results showed that preoperative serum carbohydrate antigen 19-9 level was correlated with poorer prognoses, and postoperative serum CEA >= 5 ng/mL was significantly correlated with a worse prognosis. At the time of diagnosis of re-recurrence, there was a high rate of serum CEA elevation.
DISEASES OF THE COLON & RECTUM
(2023)
Article
Oncology
Masashi Kanai, Takahisa Kawaguchi, Masahito Kotaka, Dai Manaka, Junichi Hasegawa, Akinori Takagane, Yoshinori Munemoto, Takeshi Kato, Tetsuya Eto, Tetsuo Touyama, Takanori Matsui, Katsunori Shinozaki, Shigemi Matsumoto, Tsunekazu Mizushima, Masaki Mori, Junichi Sakamoto, Atsushi Ohtsu, Takayuki Yoshino, Shigetoyo Saji, Fumihiko Matsuda
Summary: This study aimed to investigate the impact of DPYD genotype on FP-related toxicities in an Asian population. The results showed that the DPYD genotype registered in CPIC plays a minor role in FP-related toxicities in Asians.
Article
Oncology
Yusuke Oji, Naoki Kagawa, Hideyuki Arita, Norifumi Naka, Ken-ichiro Hamada, Hidetatsu Outani, Yasushi Shintani, Yoshito Takeda, Eiichi Morii, Kenzo Shimazu, Motoyuki Suzuki, Sumiyuki Nishida, Jun Nakata, Akihiro Tsuboi, Miki Iwai, Sae Hayashi, Rin Imanishi, Sayaka Ikejima, Mizuki Kanegae, Masahiro Iwamoto, Mayu Ikeda, Kento Yagi, Haruka Shimokado, Hiroko Nakajima, Kana Hasegawa, Soyoko Morimoto, Fumihiro Fujiki, Akira Nagahara, Atsushi Tanemura, Yutaka Ueda, Tsunekazu Mizushima, Masato Ohmi, Takayuki Ishida, Manabu Fujimoto, Norio Nonomura, Tadashi Kimura, Hidenori Inohara, Seiji Okada, Haruhiko Kishima, Naoki Hosen, Atsushi Kumanogoh, Yoshihiro Oka, Haruo Sugiyama
Summary: Therapeutic options for rare cancers are limited, necessitating the development of novel strategies. Our clinical study showed that a biweekly WT1 Trio peptide vaccine induced stronger immune responses against WT1 compared to a weekly WT1-CTL peptide vaccine. The vaccine was confirmed to be safe, with only one patient experiencing severe adverse events. Fifteen out of 45 patients achieved stable disease after 3 months of treatment, suggesting that WT1-targeted immunotherapy may be a potential strategy for rare cancers.
Article
Biochemistry & Molecular Biology
Masatoshi Nomura, Yuichiro Miyake, Akira Inoue, Yuhki Yokoyama, Nanaka Noda, Shihori Kouda, Tsuyoshi Hata, Takayuki Ogino, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto
Summary: This study developed a dielectrophoresis-based micropore system to analyze circulating tumor cells (CTCs) in colorectal cancer (CRC) patients. CTCs were successfully captured and identified using this system, and mutations in KRAS, BRAF, and PIK3CA genes were examined. The presence of CTCs was associated with lymph node metastasis, and novel mutations were found in CTCs that were not detected in the corresponding primary tumors. This method has potential applications for various tumor types.
Article
Oncology
Masatoshi Kitakaze, Mamoru Uemura, Tomoaki Hara, Ryota Chijimatsu, Daisuke Motooka, Toshiro Hirai, Masamitsu Konno, Daisuke Okuzaki, Yuki Sekido, Tsuyoshi Hata, Takayuki Ogino, Hidekazu Takahashi, Norikatsu Miyoshi, Ken Ofusa, Tsunekazu Mizushima, Hidetoshi Eguchi, Yuichiro Doki, Hideshi Ishii
Summary: This study found that the number of CD103(+)/CD8(+) tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in colorectal cancer (CRC). Additionally, they identified the expression of ZNF683 as a candidate marker for cancer-specific tissue-resident memory T (Trm) cells. The activation of Trm cells in tumors involves IFN-gamma and TCR signaling, as well as ZNF683 expression, which could be promising targets for cancer immunity regulation.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Masatoshi Nomura, Yuhki Yokoyama, Daishi Yoshimura, Yasuhisa Minagawa, Aki Yamamoto, Yukiko Tanaka, Naoko Sekiguchi, Daiki Marukawa, Momoko Ichihara, Hiroaki Itakura, Kenichi Matsumoto, Yoshihiro Morimoto, Hideo Tomihara, Akira Inoue, Takayuki Ogino, Norikatsu Miyoshi, Hidekazu Takahashi, Hidenori Takahashi, Mamoru Uemura, Shogo Kobayashi, Tsunekazu Mizushima, Takahisa Anada, Masaki Mori, Yuichiro Doki, Masaru Tanaka, Hidetoshi Eguchi, Hirofumi Yamamoto
Summary: In this study, a simple detection method using poly(2-methoxyethyl acrylate) (PMEA)-coated plates was established for the detection of circulating tumor cells (CTCs) in colorectal cancer (CRC) patients' blood samples. The efficacy of PMEA coating was confirmed through adhesion and spike tests. The study enrolled 41 CRC patients, and CTCs were successfully captured using PMEA. Cytological examination and cell culture provided valuable information about the presence and characteristics of CTCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Yoshiki Kajiwara, Arata Takahashi, Hideki Ueno, Yoshihiro Kakeji, Hiroshi Hasegawa, Susumu Eguchi, Takanori Goi, Akio Saiura, Akira Sasaki, Shuji Takiguchi, Hiroya Takeuchi, Chie Tanaka, Masaji Hashimoto, Naoki Hiki, Akihiko Horiguchi, Satoru Matsuda, Tsunekazu Mizushima, Shigeru Marubashi, Mitsukazu Gotoh, Hiroyuki Konno, Hiroyuki Yamamoto, Hiroaki Miyata, Yasuyuki Seto, Yuko Kitagawa
Summary: This study summarizes the data of gastroenterological surgery in the National Clinical Database (NCD) of Japan from 2011 to 2020. It found that the number of surgeries has been increasing in the past decade, except for a decrease in 2020 due to the COVID-19 pandemic. The average age of surgical patients is steadily increasing, with more than 20% of patients aged 80 years or older. Overall, Japanese gastroenterological surgeries have shown good safety.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)