The Kinetochore Is an Enhancer of Pericentric Cohesin Binding

The recruitment of cohesins to pericentric chromatin in some organisms appears to require heterochromatin associated with repetitive DNA. However, neocentromeres and budding yeast centromeres lack flanking repetitive DNA, indicating that cohesin recruitment occurs through an alternative pathway. Here, we demonstrate that all budding yeast chromosomes assemble cohesin domains that extend over 20–50 kb of unique pericentric sequences flanking the conserved 120-bp centromeric DNA. The assembly of these cohesin domains requires the presence of a functional kinetochore in every cell cycle. A similar enhancement of cohesin binding was also observed in regions flanking an ectopic centromere. At both endogenous and ectopic locations, the centromeric enhancer amplified the inherent levels of cohesin binding that are unique to each region. Thus, kinetochores are enhancers of cohesin association that act over tens of kilobases to assemble pericentric cohesin domains. These domains are larger than the pericentric regions stretched by microtubule attachments, and thus are likely to counter microtubule-dependent forces. Kinetochores mediate two essential segregation functions: chromosome movement through microtubule attachment and biorientation of sister chromatids through the recruitment of high levels of cohesin to pericentric regions. We suggest that the coordination of chromosome movement and biorientation makes the kinetochore an autonomous segregation unit

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed . in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45. nm to 1.5. nm) and a decrease in the D-period length (from 67.5. nm to 67.1. nm) in aged tissues, both using the ribose model of . in vitro glycation and in native human probes. Multiscale mechanical analysis of . in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue

Molecular taxonomy of bambusicolous fungi: Tetraplosphaeriaceae, a new pleosporalean family with Tetraploa-like anamorphs

A new pleosporalean family Tetraplosphaeriaceae is established to accommodate five new genera; 1) Tetraplosphaeria with small ascomata and anamorphs belonging to Tetraploa s. str., 2) Triplosphaeria characterised by hemispherical ascomata with rim-like side walls and anamorphs similar to Tetraploa but with three conidial setose appendages, 3) Polyplosphaeria with large ascomata surrounded by brown hyphae and anamorphs producing globose conidia with several setose appendages, 4) Pseudotetraploa, an anamorphic genus, having obpyriform conidia with pseudosepta and four to eight setose appendages, and 5) Quadricrura, an anamorphic genus, having globose conidia with one or two long setose appendages at the apex and four to five short setose appendages at the base. Fifteen new taxa in these genera mostly collected from bamboo are described and illustrated. They are linked by their Tetraploa s. l. anamorphs. To infer phylogenetic placement in the Pleosporales, analyses based on a combined dataset of small- and large-subunit nuclear ribosomal DNA (SSU+LSU nrDNA) was carried out. Tetraplosphaeriaceae, however, is basal to the main pleosporalean clade and therefore its relationship with other existing families was not completely resolved. To evaluate the validity of each taxon and to clarify the phylogenetic relationships within this family, further analyses using sequences from ITS-5.8S nrDNA (ITS), transcription elongation factor 1-α (TEF), and β-tubulin (BT), were also conducted. Monophyly of the family and that of each genus were strongly supported by analyses based on a combined dataset of the three regions (ITS+TEF+BT). Our results also suggest that Tetraplosphaeria (anamorph: Tetraploa s. str.) is an ancestral lineage within this family. Taxonomic placement of the bambusicolous fungi in Astrosphaeriella, Kalmusia, Katumotoa, Massarina, Ophiosphaerella, Phaeosphaeria, Roussoella, Roussoellopsis, and Versicolorisporium, are also discussed based on the SSU+LSU phylogeny

Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen

優れたB型肝炎予防ワクチン開発に成功 --既存ワクチンの弱点克服へ--. 京都大学プレスリリース. 2022-09-07.Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes

Structure of Protein Interaction Networks and Their Implications on Drug Design

Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects

Comparison of trauma systems in Asian countries: a cross-sectional study.

OBJECTIVE: This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). METHODS: Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. RESULTS: Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). CONCLUSION: Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies

Evidence for Direct CP Violation in B±→ηh±B^\pm \to \eta h^\pm and Observation of B0→ηK0B^0 \to \eta K^0

We report measurements of the branching fractions and CP asymmetries for B^+- -> eta h^+- (h = K or pi) and the observation of the decay B^0 -> eta K^0 from the final data sample of 772x10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e^+e^- collider. The measured branching fractions are Br(B^+- -> eta K^+-) = (2.12 +- 0.23 +- 0.11)x10^-6}, Br(B^+- -> eta pi^+-) = (4.07 +- 0.26 +- 0.21)x10^{-6} and Br(B^0 -> eta K^0) = (1.27^{+0.33}_{-0.29} +- 0.08)x10^-6, where the last decay is observed for the first time with a significance of 5.4 standard deviations (\sigma). We also find evidence for CP violation in the charged B modes, A_{CP}(B^+- -> eta K^+-) = -0.38 +- 0.11 +- 0.01 and A_{CP}(B^+- -> eta pi^+- = -0.19 +- 0.06 +- 0.01 with significances of 3.8 sigma and 3.0 sigma, respectively. For all measurements, the first and second uncertainties are statistical and systematic, respectively.Comment: 6 pages, 3 figures, 1 tabl