The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients.     

Prognostic Value of FDG PET Imaging in Patients with Laryngeal Cancer

Background and Purpose

To investigate the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer.

Materials and Methods

The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method.

Results

The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧4) had a significantly lower progression-free survival rate than those with a low SUVmax (<4; p<0.0001).

Conclusions

The pretreatment SUVmax of nodal disease in patients with laryngeal cancer is prognostic for recurrence.     

Synthesis of Cyclic ADP-Carbocylcic-Xylose and its 3′′- O O -Methyl Analogue as Stable and Potent Ca2+-Mobilizing Agents

We previously showed that 3″-deoxy-cyclic ADP-carbocyclic-ribose (3″-deoxy-cADPcR, 3) is a stable and highly potent analogue of cyclic ADP-ribose (cADPR, 1), a Ca²⁺-mobilizing second messenger. From these results, we newly designed another 3″-modified analogues of cADPcR and identified the N1-“xylo”-type carbocyclic analogue, i.e., cADPcX (4), as one of the most potent cADPR-related compounds reported so far.     

Cleavage of Short RNAs Containing Higher Ordered Structures by Hammerhead Ribozymes

Abstract

Cleavage of two types of secondary structure-forming substrates by their cognate hammerhead ribozymes were studied by measuring their kinetic parameters. A substrate with a self-complementary structure (GGUCCUAGGA, CL-3) was slowly cleaved by a two-stranded ribozyme. An isomer having no complementary sequence (GGUCGUAGCA, CL-3N) was cleaved more than 10 times faster than the self-complementary substrate. A newly designed ribozyme which contained a stable loop and stem cleaved the self-complementary decamer 40 times faster than the two-stranded ribozyme. A 15 mer which derived from a ras mRNA was found to have an intermolecular base pairs and was used to design more efficient ribozymes. Gel mobility shift assay was employed to investigate the binding properties of substrates to ribozymes. Investigations of the thermodynamic stability of the ribozyme-substrate complex are essential in the design of ribozymes that efficiently cleave RNA.

     

Seasonal development of five Cephaleuros species (Trentepohliaceae,Chlorophyta) on the leaves of woody plants and the behaviors of their gametes and zoospores

The infection cycle of five Cephaleuros species – C. aucubae, C. biolophus, C. japonicus, C. microcellularis, and C. virescens – was clarified by investigating seasonal development and gamete and zoospore behavior at study sites in Matsue, Shimane Prefecture, Japan. Fresh thalli or lesions appeared on the leaves of various woody plants from August and continued to develop in general from April to September in the following year. Gametangia and zoosporangia matured on 2‐ and 3‐year‐old leaves. Gametes were released in C. microcellularis samples collected from late March to late May and in samples of the other four species collected from late April to late July. Zoospores were released in C. biolophus, C. japonicus, and C. virescens samples collected from mid‐May to early August. In the present study, gametes did not conjugate but germinated like zoospores to produce new plants. After inoculation with zoospores and gametes that behave as asexual spores, fresh thalli or lesions became evident in 2–5 months following inoculation and gametes and zoospores were produced on the developed thalli or lesions the following year; one cycle of the infection was completed per year in the study area.     

Kinematic adjustments to arboreal locomotion in Japanese macaques (Macaca fuscata)

Primates - Although biomechanical adaptations to arboreal locomotion have been well investigated in primates and other mammals in laboratory settings, the results are not consistent, and more...     

Identification of TMEM45B as a protein clearly showing thermal aggregation in SDS-PAGE gels and dissection of its amino acid sequence responsible for this aggregation

SDS-PAGE is one of the most powerful experimental techniques used for the separation of proteins, and most proteins are separated according to their molecular size by this technique. However, exceptional proteins showing abnormal behavior in SDS-PAGE gels are known to exist. Thermal aggregation, rarely observed with membrane proteins, is one of the exceptional behaviors of proteins during SDS-PAGE, but detailed characterization of this aggregation has not yet been achieved. In the present study, we found that a putative membrane protein, TMEM45B, very clearly showed properties of thermal aggregation when it was expressed in COS7 cells and subjected to SDS-PAGE. We dissected the region of TMEM45B responsible for this aggregation, and found that of the seven putative transmembrane domains, a region comprising the 4th to 7th ones was essential for the thermal aggregation properties. We also demonstrated that these transmembrane domains, 4th to 7th, of TMEM45B conferred thermal aggregation properties on other proteins, by fusing this amino acid sequence to target proteins. The molecular mechanism causing thermal aggregation by TMEM45B is still uncertain, but TMEM45B could be utilized as a nice model to show clear thermal aggregation in SDS-PAGE gels.     

Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G(1) and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus.