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1.
Occup Med (Lond) ; 74(4): 283-289, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38682567

ABSTRACT

BACKGROUND: Presenteeism refers to being present at work but experiencing reduced productivity due to health problems, and has been known to be related to sleep loss. Workers commonly sleep longer on days off than on workdays, and presenteeism may be reduced with extended sleep on days off. AIMS: This study aimed to determine the association between sleep duration both on workdays and days off and presenteeism. METHODS: The participants were 1967 workers who engaged in work for 5 days and rested for 2 days weekly. Sleep duration was classified into less than 6 hours (short; S), 6-8 hours (medium; M), and 9 hours or longer (long; L), for workdays and days off, respectively. Presenteeism was assessed using the World Health Organization Health and Work Performance Questionnaire. RESULTS: On both workdays and days off, compared to medium sleep duration, short sleep duration was significantly associated with increased odds of presenteeism. The odds of presenteeism were significantly increased for S-S (odds ratio [OR] 2.17, 95% confidence interval [CI]1.40-3.37), S-M (OR 1.59, 95% CI 1.14-2.22), S-L (OR 2.71, 95% CI 1.05-7.00), and M-S (OR 6.82, 95% CI 2.71-17.17) combined sleep duration for workdays and days off, respectively, compared to an M-M (reference). CONCLUSIONS: Sleep loss on workdays cannot be compensated for with longer sleep on days off. This study suggests that sufficient sleep duration on both workdays and days off is important for reducing presenteeism.


Subject(s)
Presenteeism , Sleep , Humans , Presenteeism/statistics & numerical data , Male , Female , Adult , Surveys and Questionnaires , Sleep/physiology , Middle Aged , Time Factors , Work Schedule Tolerance/psychology , Work Schedule Tolerance/physiology , Sleep Deprivation/complications , Sleep Deprivation/psychology , Efficiency , Absenteeism , Sleep Duration
2.
Science ; 376(6595): 857-860, 2022 05 20.
Article in English | MEDLINE | ID: mdl-35587979

ABSTRACT

In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide Phytophthora infestans-ceramide D (Pi-Cer D) from the plant pathogenic oomycete P. infestans triggers defense responses in Arabidopsis. Pi-Cer D is cleaved by an Arabidopsis apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl-branched sphingoid base is recognized by a plasma membrane lectin receptor-like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2). 9-Methyl-branched sphingoid base is specific to microbes and induces plant immune responses by physically interacting with RDA2. Loss of RDA2 or NCER2 function compromised Arabidopsis resistance against an oomycete pathogen. Thus, we elucidated the recognition mechanisms of pathogen-derived lipid molecules in plants.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Ceramides , Host-Pathogen Interactions , Neutral Ceramidase , Phytophthora infestans , Plant Diseases , Arabidopsis/genetics , Arabidopsis/immunology , Arabidopsis/microbiology , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Ceramides/metabolism , Neutral Ceramidase/genetics , Neutral Ceramidase/metabolism , Phytophthora infestans/pathogenicity , Plant Diseases/immunology , Plant Diseases/microbiology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Receptors, Mitogen/genetics , Receptors, Mitogen/metabolism
3.
Science ; 375(6584): 1011-1016, 2022 03 04.
Article in English | MEDLINE | ID: mdl-35143255

ABSTRACT

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

4.
Sci Rep ; 9(1): 13349, 2019 09 16.
Article in English | MEDLINE | ID: mdl-31527702

ABSTRACT

Species of the fungal genus Colletotrichum are among the most devastating pathogens of agricultural crops in the world. Based on DNA sequence data (ITS, GAPDH, CHS-1, ACT, TUB2) and morphology, we revealed Colletotrichum isolates infecting the oil crop Perilla frutescens, commonly known as shiso, to represent a previously unknown species of the C. destructivum species complex and described it as C. shisoi. We found that C. shisoi appears to be able to adopt a hemibiotrophic lifestyle, characterised by the formation of biotrophic hyphae followed by severe necrotic lesions on P. frutescens, but is less virulent on Arabidopsis, compared to its close relative C. higginsianum which also belongs to the C. destructivum species complex. The genome of C. shisoi was sequenced, annotated and its predicted proteome compared with four other Colletotrichum species. The predicted proteomes of C. shisoi and C. higginsianum, share many candidate effectors, which are small, secreted proteins that may contribute to infection. Interestingly, C. destructivum species complex-specific secreted proteins showed evidence of increased diversifying selection which may be related to their host specificities.


Subject(s)
Colletotrichum/genetics , Fungal Proteins/genetics , Genome, Fungal/genetics , Perilla frutescens/microbiology , Base Sequence , Colletotrichum/classification , Colletotrichum/isolation & purification , Colletotrichum/pathogenicity , Crops, Agricultural/microbiology , Genomics , Japan , Multilocus Sequence Typing , Phylogeny , Plant Diseases/microbiology , Proteome/genetics
5.
J Hosp Infect ; 103(3): 341-348, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31078633

ABSTRACT

BACKGROUND: Nosocomial infections by respiratory viruses undetected by rapid tests are not often diagnosed. For paediatric patients with background diseases, nosocomial infection could be fatal. AIM: To determine the relationship between developing symptoms by respiratory viruses undetectable by rapid tests and respiratory risks and to improve the management of infection control. METHODS: Two episodes of nosocomial infection by human bocavirus (HBoV) and human rhinovirus (HRV) were retrospectively investigated in a tertiary hospital paediatric ward in Japan. Viruses were identified by polymerase chain reaction to determine infection control management. When viruses of the same species were detected from different patients, the virus homology was investigated. The relationship between respiratory risks and developing symptoms was statistically investigated. FINDINGS: Three and four patients with respiratory risks in the HBoV and HRV outbreaks, respectively, developed respiratory symptoms. The nucleotide sequences of two patients in the HBoV outbreak and all four patients in the HRV outbreak were phylogenetically close. In both outbreaks, the patients with respiratory risks developed significantly more symptoms than those without any risk (P = 0.035 and 0.018, respectively). After the patients with respiratory infection were separated from those with respiratory risks, no additional nosocomial infection occurred. CONCLUSION: Patients with respiratory risks easily develop respiratory symptoms and acquire severe symptoms of nosocomial infection by those viruses. In a paediatric ward, we should adopt not only standard precautions but also isolation management of the patients with respiratory symptoms, even if they have negative results in rapid tests.


Subject(s)
Cross Infection/epidemiology , Human bocavirus/isolation & purification , Parvoviridae Infections/epidemiology , Picornaviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , Rhinovirus/isolation & purification , Child, Preschool , Female , Hospitals, Pediatric , Human bocavirus/classification , Human bocavirus/genetics , Humans , Infant , Japan/epidemiology , Male , Molecular Epidemiology , Polymerase Chain Reaction , Retrospective Studies , Rhinovirus/classification , Rhinovirus/genetics , Risk Factors , Tertiary Care Centers
6.
Mol Plant Microbe Interact ; 32(9): 1088-1090, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30893003

ABSTRACT

Colletotrichum orbiculare species complex fungi are hemibiotrophic plant pathogens that cause anthracnose of field crops and weeds. Members of this group have genomes that are remarkably expanded relative to other Colletotrichum fungi and compartmentalized into AT-rich, gene-poor and GC-rich, gene-rich regions. Here, we present an updated version of the C. orbiculare genome, as well as draft genomes of three other members from the C. orbiculare species complex: the alfalfa pathogen C. trifolii, the prickly mallow pathogen C. sidae, and the burweed pathogen C. spinosum. The data reported here will be important for comparative genomics analyses to identify factors that play a role in the evolution and maintenance of the expanded, compartmentalized genomes of these fungi, which may contribute to their pathogenicity.


Subject(s)
Colletotrichum , Genome, Fungal , Colletotrichum/classification , Colletotrichum/genetics , Colletotrichum/pathogenicity , Plant Diseases/microbiology , Virulence/genetics
7.
Surg Endosc ; 33(6): 1769-1776, 2019 06.
Article in English | MEDLINE | ID: mdl-30291444

ABSTRACT

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.


Subject(s)
Colorectal Neoplasms/surgery , Operative Time , Aged , Aged, 80 and over , Colectomy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Incidence , Japan/epidemiology , Laparoscopy , Male , Middle Aged , Postoperative Complications/epidemiology , Propensity Score , Retrospective Studies , Survival Analysis
8.
Sci Rep ; 8(1): 7041, 2018 May 04.
Article in English | MEDLINE | ID: mdl-29728613

ABSTRACT

It is now well established that the microstructure of Fe-based chalcogenide K x Fe2-ySe2 consists of, at least, a minor (~15 percent), nano-sized, superconducting K s Fe2Se2 phase and a major (~85 percent) insulating antiferromagnetic K2Fe4Se5 matrix. Other intercalated A1-xFe2-ySe2 (A = Li, Na, Ba, Sr, Ca, Yb, Eu, ammonia, amide, pyridine, ethylenediamine etc.) manifest a similar microstructure. On subjecting each of these systems to a varying control parameter (e.g. heat treatment, concentration x,y, or pressure p), one obtains an exotic normal-state and superconducting phase diagram. With the objective of rationalizing the properties of such a diagram, we envisage a system consisting of nanosized superconducting granules which are embedded within an insulating continuum. Then, based on the standard granular superconductor model, an induced variation in size, distribution, separation and Fe-content of the superconducting granules can be expressed in terms of model parameters (e.g. tunneling conductance, g, Coulomb charging energy, E c , superconducting gap of single granule, Δ, and Josephson energy J = πΔg/2). We show, with illustration from experiments, that this granular scenario explains satisfactorily the evolution of normal-state and superconducting properties (best visualized on a [Formula: see text] phase diagram) of A x Fe2-ySe2 when any of x, y, p, or heat treatment is varied.

9.
J Hosp Infect ; 100(2): 211-213, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29452243

ABSTRACT

Removal of bacteria by handwashing with ozonated water was evaluated using the ASTM E1174 standard test method. Thirty healthy volunteers were assigned randomly to three groups: ozonated water, antimicrobial soap and water, and non-antimicrobial soap and water. A 3 log10 cfu reduction was achieved by washing hands with ozonated water or antimicrobial soap and water. However, ozonated water was not significantly superior to non-antimicrobial soap and water. Ozonated water may remove bacteria from the hands to at least a similar extent as that by non-antimicrobial soap and water in the absence of visible dirt or body fluid contamination.


Subject(s)
Bacteria/drug effects , Disinfectants/pharmacology , Hand Disinfection/methods , Hand/microbiology , Ozone/pharmacology , Water/pharmacology , Adolescent , Adult , Aged , Bacteria/growth & development , Bacteria/isolation & purification , Colony Count, Microbial , Female , Healthy Volunteers , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
10.
Exp Appl Acarol ; 73(3-4): 353-363, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29185081

ABSTRACT

Previous studies on the spider mite Eotetranychus smithi Pritchard & Baker have shown that diapause in eggs is induced by low temperature alone and that females developed at ≤ 17.5 °C laid diapause eggs, regardless of the photoperiod. In this study, diapause eggs were kept at 5 °C and a photoperiod of 16L:8D for 0-120 days and then maintained at 25 °C to know the effect of chilling on diapause termination. Diapause eggs mostly hatched when they were maintained at 25 °C after chilling for 30-90 days at 5 °C, which suggests that diapause termination is favored by low temperatures. To clarify the hatching conditions after diapause termination, diapause eggs kept at 5 °C for 45 days were subsequently maintained at various constant temperatures (from 15 to 25 °C) under a long-day photoperiod (16L:8D). The hatchability at all temperatures tested was high (> 90%) and did not significantly differ among the high temperatures. Duration of embryonic development was shorter with increasing warming temperature after chilling. The lower thermal threshold (t) and thermal constant (k) for post-diapause egg development were 10.5 °C and 76.9 degree-days, respectively. Females, which developed from diapause eggs that were chilled at 5 °C for 45 days and then maintained at 15 °C, laid only non-diapause eggs, which indicates that they were prevented from re-entering diapause even under diapause-inducing conditions (15 °C). Thus, temperature is the main factor to control diapause termination and post-diapause development, which has also been found for other spider mites that enter diapause at the egg stage.


Subject(s)
Diapause , Ovum/growth & development , Tetranychidae/growth & development , Animals , Cold Temperature , Female
11.
Transplant Proc ; 49(7): 1644-1648, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28838456

ABSTRACT

Biliary complications, such as stricture or obstruction, after living-donor liver transplantation (LDLT) remain major problems to be solved. Magnetic compression anastomosis (MCA) is a minimally invasive method of biliary anastomosis without surgery in patients with biliary stricture or obstruction. A 66-year-old woman had undergone LDLT for end-stage liver disease for primary biliary cholangitis 20 months previously at another hospital. Computerized tomography showed dilation of the intrahepatic bile duct (B2). Because B2 was invisible with the use of endoscopic retrograde cholangiopancreatography, percutaneous transhepatic biliary drainage (PTBD) was performed for treatment of cholangitis. The rendezvous technique failed because a guidewire could not pass through the biliary stricture. Therefore, we decided to perform MCA. A parent magnet was endoscopically placed distally in the common bile duct of the stricture, and a daughter magnet attached to a guidewire was inserted proximally through the fistula tract of the PTBD. Both magnets were positioned across the stricture, and the 2 magnets were pulled to each other by magnetic power, to sandwich the stricture. By 14 days after MCA, a fistula between B2 and the common bile duct was created. At 28 days after MCA, the magnets were removed distally and a 16-French tube was placed across the fistula. At 7 months after MCA, that tube was removed. In conclusion, when a conventional endoscopic or percutaneous approach including the rendezvous technique fails, MCA is a good technique for biliary stricture after LDLT.


Subject(s)
Bile Ducts/surgery , Biliary Tract Surgical Procedures/methods , Liver Transplantation/adverse effects , Magnetics , Postoperative Complications/surgery , Aged , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Bile Ducts/diagnostic imaging , Bile Ducts/pathology , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/surgery , Biliary Tract Surgical Procedures/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholangitis/etiology , Cholangitis/pathology , Cholangitis/surgery , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Drainage/adverse effects , Drainage/methods , End Stage Liver Disease/etiology , End Stage Liver Disease/surgery , Female , Humans , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/surgery , Liver Transplantation/methods , Living Donors , Postoperative Complications/etiology , Postoperative Complications/pathology , Tomography, X-Ray Computed
12.
J Dent Res ; 96(12): 1422-1429, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28732182

ABSTRACT

Loss-of-function mutations in the Ca2+ release-activated Ca2+ channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 ( Stim1 cKO [conditional knockout]), Stim2 ( Stim2 cKO), and Stim1 and Stim2 ( Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control ( Stim1/2fl/fl) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.


Subject(s)
Ameloblasts/physiology , Amelogenesis/genetics , Stromal Interaction Molecule 1/genetics , Amelogenesis Imperfecta/genetics , Animals , Calcium Channels/genetics , Dental Enamel Proteins/genetics , Genotype , Immunohistochemistry , Mice , Mice, Transgenic , Microscopy, Electron, Scanning , Phenotype , Polymerase Chain Reaction , X-Ray Microtomography
13.
Exp Appl Acarol ; 72(3): 205-227, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28707033

ABSTRACT

The impact of daily temperature fluctuations on arthropod life history parameters is inadequately studied compared with the ample amount of research that has been conducted on the effects of constant temperatures. Fluctuating temperatures are likely to be more realistic, as they are ecologically more similar to what these arthropods experience in nature. Here, we compared the impact of 11 constant temperatures that ranged from 10 to 35 °C with fluctuating temperatures with the same corresponding mean temperature and an amplitude of 10 °C between high (12 h) and low (12 h) temperatures on the development and life history parameters of Tetranychus urticae under continuous light conditions. No eggs hatched at constant 10 °C, whereas 81.5% of eggs successfully completed development at fluctuating 10 °C (15/5 °C). Egg-to-female adult development was faster under fluctuating temperatures from 12.5 to 27.5 °C than under constant temperatures, whereas the opposite trend was observed at >30 °C. The lower thermal thresholds (T) were 11.63 and 8.63 °C, and thermal constants (K) were 127.81 and 150.69 degree-days for egg-to-female adults at constant and fluctuating temperatures, respectively. The numbers of oviposition days were significantly higher at fluctuating 15 °C than at the corresponding constant temperature, whereas the opposite trend was observed from 20 to 30 °C. The intrinsic rate of increase (r) was higher at fluctuating than at constant 15 °C. The net reproductive rate (R 0) was also higher at fluctuating than at constant 15 and 35 °C, but showed an opposite trend at 20 and 25 °C. We conclude that fluctuating temperatures should be considered to accurately predict spider mite population dynamics in nature.


Subject(s)
Life Cycle Stages/physiology , Oviposition/physiology , Temperature , Tetranychidae/physiology , Animals , Female , Population Dynamics , Reproduction
14.
Transplant Proc ; 49(5): 1087-1091, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28583533

ABSTRACT

BACKGROUND: Graft regeneration and functional recovery after reperfusion of transplanted graft are very important for successful living donor liver transplantation (LDLT). The aim of this study was to evaluate the significance of postoperative portal venous velocity (PVV) in short-term recovery of graft function in LDLT. PATIENTS AND METHODS: From February 2007 through December 2015, we performed 17 primary LDLTs, which were included in the present study. The patients ranged in age from 12 to 65 years (mean: 50 years), and 11 were female patients. Postoperatively, Doppler ultrasonography was performed daily to measure PVV (cm/s), and liver function parameters were measured daily. The change in PVV (ΔPVV) was defined as follows: ΔPVV = PVV on postoperative day (POD) 1 - PVV on POD 7. Maximal value of serum aspartate aminotransferase (ASTmax) and maximal value of serum alanine transaminase (ALTmax) at 24 hours after graft reperfusion were used as parameters of reperfusion injury. Correlation analyses were performed as follows: (1) correlation of ΔPVV and PVV on POD 1 (PVV-POD 1) with the values such as ASTmax, ALTmax, other liver function parameters on POD 7 and graft regeneration rate; (2) correlation of ASTmax and ALTmax with other liver function parameters on POD 7. RESULTS: ΔPVV significantly correlated with the values of serum total bilirubin (P < .01), prothrombin time (P < .01), and platelet count (P < .05), and PVV-POD 1 significantly correlated with the values of serum total bilirubin (P < .05) and prothrombin time (P < .05). CONCLUSION: ΔPVV and PVV-POD 1 may be useful parameters of short-term functional recovery of the transplant liver in LDLT.


Subject(s)
Liver Function Tests/methods , Liver Transplantation , Living Donors , Portal Vein , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult
15.
Genome Announc ; 5(10)2017 Mar 09.
Article in English | MEDLINE | ID: mdl-28280027

ABSTRACT

Colletotrichum chlorophyti is a fungal pathogen that infects various herbaceous plants, including crops such as legumes, tomato, and soybean. Here, we present the genome of C. chlorophyti NTL11, isolated from tomato. Analysis of this genome will allow a clearer understanding of the molecular mechanisms underlying fungal host range and pathogenicity.

16.
Phys Chem Chem Phys ; 19(7): 5310-5317, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28155939

ABSTRACT

A nerve conduction model is constructed by using some liquid-membrane cells that mimic the function of the K+ and Na+ channels. By imitating two types of Na+ channels (ligand-gated Na+ channels and voltage-gated Na+ channels), a new mechanism for the directional propagation of the action potential along the axon toward the axon terminal is proposed. When the nerve cell is excited by an external (outer) stimulus, it can be presumed that the ligand-gated channels work as power sources at the synapse to propagate the change in the membrane potential, and then the voltage-gated channels locally assist the propagation at each site of the axon (nodes of Ranvier).


Subject(s)
Action Potentials/physiology , Models, Biological , Neural Conduction/physiology , Potassium Channels/metabolism , Sodium Channels/metabolism
17.
Rev Sci Instrum ; 87(7): 076103, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27475610

ABSTRACT

A novel diamond anvil cell suitable for electrical transport measurements under high pressure has been developed. A boron-doped metallic diamond film was deposited as an electrode on a nano-polycrystalline diamond anvil using a microwave plasma-assisted chemical vapor deposition technique combined with electron beam lithography. The maximum pressure that can be achieved by this assembly is above 30 GPa. We report electrical transport measurements of Pb up to 8 GPa. The boron-doped metallic diamond electrodes showed no signs of degradation after repeated compression.

18.
Drug Res (Stuttg) ; 66(2): 74-81, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26158794

ABSTRACT

OBJECTIVE: Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers. METHODS: A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men. Cmax, AUCinf, and cumulative urine glucose excretion after co-administration of tofogliflozin and each of the anti-T2DM drugs was evaluated relative to the values of those parameters after administration of each drug alone. RESULTS: None of the anti-T2DM drugs had any effect on tofogliflozin exposure. Tofogliflozin had no or little effect on the exposure of any anti-T2DM drug. No anti-T2DM drug had any major effect on the cumulative urine glucose excretion induced by tofogliflozin. There were no safety concerns evident after administration of any drug alone or in co-administration. CONCLUSIONS: Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers.


Subject(s)
Benzhydryl Compounds/pharmacology , Benzhydryl Compounds/pharmacokinetics , Diabetes Mellitus, Type 2/drug therapy , Glucosides/pharmacology , Glucosides/pharmacokinetics , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/pharmacokinetics , Sodium-Glucose Transporter 2 Inhibitors , 1-Deoxynojirimycin/analogs & derivatives , 1-Deoxynojirimycin/pharmacokinetics , 1-Deoxynojirimycin/pharmacology , Adult , Cyclohexanes/pharmacokinetics , Cyclohexanes/pharmacology , Diabetes Mellitus, Type 2/blood , Drug Interactions , Glucose/analysis , Healthy Volunteers , Humans , Inositol/analogs & derivatives , Inositol/pharmacokinetics , Inositol/pharmacology , Male , Metformin/pharmacokinetics , Metformin/pharmacology , Middle Aged , Nateglinide , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacokinetics , Phenylalanine/pharmacology , Pioglitazone , Sitagliptin Phosphate/pharmacokinetics , Sitagliptin Phosphate/pharmacology , Sulfonylurea Compounds/pharmacokinetics , Sulfonylurea Compounds/pharmacology , Thiazolidinediones/pharmacokinetics , Thiazolidinediones/pharmacology , Urine/chemistry , Young Adult
19.
Diabetes Obes Metab ; 17(10): 984-93, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26179482

ABSTRACT

AIM: To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. RESULTS: Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. CONCLUSIONS: A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM.


Subject(s)
Benzhydryl Compounds/administration & dosage , Body Weight/drug effects , Diabetes Mellitus, Type 2/therapy , Glucosides/administration & dosage , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Adult , Aged , Blood Glucose/drug effects , Blood Pressure/drug effects , Combined Modality Therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/urine , Diet, Diabetic , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Exercise Therapy , Fasting/blood , Female , Glycated Hemoglobin/drug effects , Glycosuria/chemically induced , Humans , Ketones/metabolism , Male , Middle Aged
20.
Science ; 349(6246): 420-4, 2015 Jul 24.
Article in English | MEDLINE | ID: mdl-26206933

ABSTRACT

Microbial life inhabits deeply buried marine sediments, but the extent of this vast ecosystem remains poorly constrained. Here we provide evidence for the existence of microbial communities in ~40° to 60°C sediment associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas compositions. Concentrations of indigenous microbial cells below 1.5 km ranged from <10 to ~10(4) cells cm(-3). Peak concentrations occurred in lignite layers, where communities differed markedly from shallower subseafloor communities and instead resembled organotrophic communities in forest soils. This suggests that terrigenous sediments retain indigenous community members tens of millions of years after burial in the seabed.


Subject(s)
Aquatic Organisms/classification , Archaea/classification , Bacteria/classification , Coal/microbiology , Geologic Sediments/microbiology , Microbial Consortia , Seawater/microbiology , Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Archaea/genetics , Archaea/metabolism , Bacteria/genetics , Bacteria/metabolism , Biomarkers/metabolism , Carbon Dioxide/metabolism , Japan , Methane/metabolism , Methanococcus/classification , Methanococcus/genetics , Methanococcus/metabolism , Methanosarcina barkeri/classification , Methanosarcina barkeri/genetics , Methanosarcina barkeri/metabolism , Pacific Ocean
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