Search

The basic region leucine zipper (bZIP) proteins form one of the largest families of transcription factors in eukaryotic cells. Despite relatively high homology between the amino acid sequences of the bZIP motifs, these proteins recognize diverse DNA sequences. Here we report the 2.0 Å resolution crystal structure of the bZIP motif of one such transcription factor, PAP1, a fission yeast AP-1-like transcription factor that binds DNA containing the novel consensus sequence TTACGTAA. The structure reveals how the Pap1-specific residues of the bZIP basic region recognize the target sequence and shows that the side chain of the invariant Asn in the bZIP motif adopts an alternative conformation in Pap1. This conformation, which is stabilized by a Pap1-specific residue and its associated water molecule, recognizes a different base in the target sequence from that in other bZIP subfamilies. [ABSTRACT FROM AUTHOR]

Piscivostatin (PVS) and acostatin are members of the disintegrin family of platelet-aggregation inhibitors found in snake venoms and are dimeric disintegrins which play different roles to the monomeric disintegrins. The crystals of PVS belonged to the P212121 space group, with unit-cell parameters a = 34.3, b = 54.4, c = 115.9 Å, and diffracted to 2.0 Å resolution. The crystals of acostatin belonged to the P21 space group, with unit-cell parameters a = 55.4, b = 69.3, c = 63.5 Å, β = 111.7°, and diffracted to 2.8 Å resolution. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinomas (NECs) are rare and highly malignant tumors with a generally poor prognosis. Carcinoembryonic antigen (CEA) is often associated with adenocarcinoma, but its significant elevation in NEC cases is unusual. A 69-year-old man was admitted to our hospital in January 2016 due to syncope induced by anemia. The patient had a hemoglobin level of 8.0 g/dL and an ileocecal mass causing small bowel obstruction on computed tomography. His CEA level was markedly elevated at 3625.4 ng/mL. A colonoscopy revealed a neoplastic lesion in the terminal ileum, leading to an emergency ileocecal resection. Pathology confirmed a NEC, positive for synaptophysin and CEA, with a Ki-67 index of 30%. The patient was diagnosed with stage IIIb NEC (pT3N2M0). A postoperative increase in CEA to 4124.6 ng/mL and metastases in the right lung and multiple lymph nodes were detected. Initial chemotherapy with irinotecan, cisplatin (IP), and octreotide acetate proved ineffective. Subsequent octreoscans showed disease progression. Switching to everolimus as second-line therapy temporarily decreased CEA levels and tumor size, but the disease progressed with cervical lymph node involvement. The patient underwent palliative radiotherapy but succumbed to disease progression in May 2018, with a final CEA level of 36,643 ng/mL. Necropsy of the cervical lymph nodes was consistent with the original surgical findings. This case highlights the aggressive nature and challenging management of NEC with significantly elevated CEA levels., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sugimoto et al.)