Search

In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment (1,2). Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A (3-12). Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate α-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the αN helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome (13). A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg80 and Gly81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome., Octasome and hemisome models have been proposed for the CENP-A nucleosome architecture (14). In the octasome model, two each of histones H2A, H2B, H4 and CENP-A form a histone octamer, [...]

Transmission is the first step for a microorganism to establish colonization in the respiratory tract and subsequent development of infectious disease. Streptococcus pneumoniae is a leading pathogen that colonizes the mucosal surfaces of the human upper respiratory tract and causes subsequent transmission and invasive infections especially in co-infection with influenza A virus. Host factors contributing to respiratory contagion are poorly understood. Transient receptor potential vanilloid (TRPV) channels have various roles in response to microoorganism. Inhibition of TRPV exacerbates invasive infection by Streptococcus pneumoniae , but it is unclear how TRPV channels influence pneumococcal transmission. Here, we describe the effect of inhibition of TRPV1 on pneumococcal transmission. We adopted a TRPV1-deficient infant mouse model of pneumococcal transmission during co-infection with influenza A virus. We also analyzed the expression of nasal mucin or pro-inflammatory cytokines. TRPV1 deficiency attenuated pneumococcal transmission and shedding during co-infection with influenza A virus. TRPV1 deficiency suppressed the expression of nasal mucin. In addition, there were increases in the expression of tumor necrosis factor-α and type I interferon, followed by the suppressed replication of influenza A virus in TRPV1-deficient mice. Inhibition of TRPV1 was shown to attenuate pneumococcal transmission by reducing shedding through the suppression of nasal mucin during co-infection with influenza A virus. Inhibition of TRPV1 suppressed nasal mucin by modulation of pro-inflammatory responses and regulation of replication of influenza A virus. TRPV1 could be a new target in preventive strategy against pneumococcal transmission., Competing Interests: The authors declare no conflict of interest.

An 82-year-old woman suddenly developed chest pain and apoplexy. Computed tomography (CT) showed acute type A aortic dissection, the true lumen in the brachicephalic artery was severely compressed by the faulse lumen. Pulsation in the either leg was not detected during induction of anesthesia. We evaluated the cerebral blood flow and lower extremity blood flow using near infrared spectroscopy (NIRS) during the operation, tissue oxygenation index (TOI) was continuously monitored during the operation. Cardiopulmonary bypass( CPB) was established by puncturing the true lumen in the ascending aorta and bicaval venous drainage. TOI was returned to normal range by CPB. Although the central repair (ascending aorta replacement) was performed, leg ischemia persisted. We performed ascending aorta-bifemoral bypass. After the operation, leg ischemia disappeared and CT revealed patency of the bypass graft. Postoperative course was uneventful without deterioration of neurological function. She was discharged 49 days after the operation.

We describe a case in which fibrinogen concentrate was useful to improve anticoagulation after aortic graft replacement. A 44-year-old man with left ventricular assist system (LVAS) underwent thoracic abdominal aortic aneurysm (TAAA) graft replacement. LVAS requires anticoagulant therapy for thromboprophylaxis. Therefore, we supposed that it would be difficult to stop bleeding in TAAA graft replacement surgery. For this reason, we planned to administer fibrinogen concentrate during the surgery. When the patient was weaned from cardiopulmonary bypass, blood fibrinogen value decreased to 58.0 mg x dl(-1). At this time, we administered fibrinogen concentrate 6 g with other blood preparations. After the administration of fibrinogen concentrate, calculated blood fibrinogen level increased immediately to 120.0 mg x dl(-1). Three hours after administration of fibrinogen concentrate, TAAA graft replacement operation was finished. Ten days after the surgery, he was discharged from the ICU. Fibrinogen concentrate might be useful in difficult hemostasis reducing consumption of blood preparations.