LOW BMI IS THE RISK OF CARDIO-VASCULAR MORTALITY WITHOUT PROGRESSION OF CKD

The paradoxical risk of BMI on mortality is known in CKD as well in dialysis populations, but studies of CVD risk in CKD including underweight is limited. We hypothesized lean CKD increase the CVD risk, contributing different factors from obese. 2,676 CKD patients recruited from 11 outpatients’ hospitals. BMI and estimated GFR (eGFR) were calculated, and change of eGFR and CVD mortality during 2 years were collected. Patients were divided by BMI under cut off value of normal, thus 7% grouped in lean subjects (BMI <18.5). Systolic blood pressure (sBP), albumin, hemoglobin, age and prevalence of diabetes were lower in lean BMI group compared to other subjects. However CVD history, urinary protein, baseline eGFR and smoking didn't differ between the groups. The lean BMI increased significantly the risk of CVD mortality, in spite of low prevalence of comorbidities and young age in unadjusted model (HR 2.38, 95%CI 1.49-5.21, p<0.01). This significance remained after adjusted for CVD risk factors, such as primary disease of CKD, age, sex, smoking, albumin, cholesterol, sBP and eGFR. On the other hand, BMI was not associated with the decline rate of eGFR. We concluded that BMI less than 18.5 was an independent predictor of CVD, and that BMI did not effect on CKD progression rate in Japanese CKD

Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2

CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by osmotic stress in CNOT2-depleted cells, indicating that CNOT2 is responsible for stress resistance of cells. Although wild-type (WT) and non-phosphorylatable CNOT2 mutants reverse this sensitivity, a phosphomimetic form of CNOT2, in which serine at the phosphorylation site is replaced with glutamate, does not have this function. We also show that mRNAs have elongated poly(A) tails in CNOT2-depleted cells and that introduction of CNOT2 WT or a non-phosphorylatable mutant, but not phosphomimetic CNOT2, renders their poly(A) tail lengths comparable to those in control HeLa cells. Consistent with this, the CCR4-NOT complex containing phosphomimetic CNOT2 exhibits less deadenylase activity than that containing CNOT2 WT. These data suggest that CCR4-NOT complex deadenylase activity is regulated by post-translational modification, yielding dynamic control of mRNA deadenylation

A novel locally operated master-slave robot system for single-incision laparoscopic surgery

Purpose: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. Material and methods: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. Results: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. Conclusion: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.ArticleMINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES. 23(6):326-332 (2014)journal articl

ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism

Eukaryotic gene expression can be spatiotemporally tuned at the post-transcriptional level by cis-regulatory elements in mRNA sequences. An important example is the AU-rich element (ARE), which induces mRNA destabilization in a variety of biological contexts in mammals and can also mediate translational control. Regulation is mediated by trans-acting factors that recognize the ARE, such as Tristetraprolin (TTP) and BRF1/ZFP36L1. Although both proteins can destabilize their target mRNAs through the recruitment of the CCR4-NOT deadenylation complex, TTP also directly regulates translation. Whether ZFP36L1 can directly repress translation remains unknown. Here, we used an in vitro translation system derived from mammalian cell lines to address this key mechanistic issue in ARE regulation by ZFP36L1. Functional assays with mutant proteins reveal that ZFP36L1 can repress translation via AU-Rich elements independent of deadenylation. ZFP36L1-mediated translation repression requires interaction between ZFP36L1 and CNOT1, suggesting that it might use a repression mechanism similar to either TPP or miRISC. However, several lines of evidence suggest that the similarity ends there. Unlike, TTP, it does not efficiently interact with either 4E-HP or GIGYF2, suggesting it does not repress translation by recruiting these proteins to the mRNA cap. Moreover, ZFP36L1 could not repress ECMV-IRES driven translation and was resistant to pharmacological eIF4A inhibitor silvestrol, suggesting fundamental differences with miRISC repression via eIF4A. Collectively, our results reveal that ZFP36L1 represses translation directly and suggest that it does so via a novel mechanism distinct from other translational regulators that interact with the CCR4-NOT deadenylase complex

Mechanisms of translational regulation by a human eIF5-mimic protein

The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNAiMet ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2Bε or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function

The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function

Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In Cnot3-depleted hearts, Atg7 expression was posttranscriptionally increased. Genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice. We further showed that in Cnot3-depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis

Horizontal spin of ratchet motor by vertical agitation

Abstract The horizontal spin of a ratchet motor by vertical vibration is reported. A macroscopic ratchet gear is placed on a granular bed, where nearly half of the gear is penetrated in the bed. The gear and granular bed are mechanically vibrated. The gear shows a random motion or one-way spin that depend on the diameter of the granules, vibration frequency, and degree of vertical motion allowed for the gear. Even when one-way spin is observed, the spin direction depends on the abovementioned factors. Although the dependency is complicated, it is deterministic because the motion or flows of granular matter determines it. The characteristics observed in the experiments are explained by a simple model that accounts for the statistical variance in the motion of the granular matter. Extraction of systematic motion from small and non-useful motions such as mechanical agitation will be developed into energy harvest technology and may facilitate the science of a spontaneously moving system in a uniform potential field