Extensive genomic diversity and selective conservation of virulence determinants in enterohemorrhagic Escherichia coli strains of O157 and non O157 serotypes

Background: Enterohemorrhagic Escherichia coli (EHEC) O157 causes severe food-borne illness in humans. The chromosome of O157 consists of 4.1 Mb backbone sequences shared by benign E. coli K-12, and 1.4 Mb O157-specific sequences encoding many virulence determinants, such as Shiga toxin genes (stx genes) and the locus of enterocyte effacement (LEE). Non-O157 EHECs belonging to distinct clonal lineages from O157 also cause similar illness in humans. According to the "parallel" evolution model, they have independently acquired the major virulence determinants, the stx genes and LEE. However, the genomic differences between O157 and non-O157 EHECs have not yet been systematically analyzed. Results: Using microarray and whole genome PCR scanning analyses, we performed a whole genome comparison of 20 EHEC strains of O26, O111, and O103 serotypes with O157. In non-O157 EHEC strains, although genome sizes were similar with or rather larger than O157 and the backbone regions were well conserved, O157-specific regions were very poorly conserved. Around only 20% of the O157- specific genes were fully conserved in each non-O157 serotype. However, the non-O157 EHECs contained a significant number of virulence genes that are found on prophages and plasmids in O157, and also multiple prophages similar to, but significantly divergent from, those in O157. Conclusion: Although O157 and non-O157 EHECs have independently acquired a huge amount of serotype- or strain-specific genes by lateral gene transfer, they share an unexpectedly large number of virulence genes. Independent infections of similar but distinct bacteriophages carrying these virulence determinants are deeply involved in the evolution of O157 and non-O157 EHECs

A Comprehensive Study of Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease

The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) remain controversial. We performed a comprehensive study to examine whether rTMS is a safe and effective treatment for PD. Twelve PD patients received rTMS once a week. The crossover study design consisted of 4-week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale, Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects. Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS scores significantly, while the sham rTMS did not. There were no significant changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems to be a safe and effective therapeutic option for PD patients, especially in a wearing-off state

Developing of higher voltage direct-current power-feeding prototype system

High efficiency power feeding systems are effective solutions for reducing ICT power consumption of ICT equipment, such as routers and servers, or high efficiency cooling systems. We developed a higher voltage direct current (HVDC) power feeding system prototype. This system is composed of a rectifier, power distribution cabinet, batteries, and ICT equipment. The configuration is similar to a -48 V DC power supply system. The output of the rectifier is 100 kW, and the output voltage is 401.4 V. We describe the advantage of an HVDC power feeding system and show that its basic characteristics are stable.INTELEC 2009 - 2009 International Telecommunications Energy Conference : Incheon, South Korea, 2009.10.18-2009.10.2

A novel digital PID controlled dc-dc converter

This paper presents the relationship between the dynamic characteristics and sampling frequency of digitally controlled dc-dc converter with a novel control method. In the proposed method, the calculation process of P and I-D controls is parallel. The sampling interval and points for I-D control are same to the conventional method. However, the sampling point for P control is quickly. The A-D converter can sample the output voltage during the short interval because the calculation process of P control is very simple and to important for transient response. The only sample data near the turn-off timing of PWM pulse is used. The simulation and experiment results of the output voltage against the step change of the load and changing the P control sampling frequency are discussed. As a result, it is revealed experimentally that the good transient response is obtained.2010 International Symposium on Power Electronics, Electrical Drives, Automation and Motion (SPEEDAM 2010) : Pisa, Italy, 2010.06.14-2010.06.1

Real-world clinical outcomes of nivolumab and taxane as a second- or later-line therapy for recurrent or unresectable advanced esophageal squamous cell carcinoma

BackgroundNivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment.MethodsIn total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety.ResultsMedian overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed.ConclusionsIn real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments

Controlling factors of large-scale harmful algal blooms with Karenia selliformis after record-breaking marine heatwaves

Unprecedented, large-scale harmful algal blooms (HABs) dominated by Karenia selliformis occurred off the southeastern coast of Hokkaido, Japan, from late September to early November 2021, about a month after intense and extensive marine heatwaves (MHWs) had subsided. The aims of the present study were to understand the mechanism of development, maintenance, and decay of the HABs as well as to investigate the effect of the MHWs on the HABs. We developed a one-dimensional, lower trophic-level ecosystem model (NEMURO+) to simulate the HABs. The model successfully simulated the 2021 HABs and indicated that their development, maintenance, and decay were controlled primarily by changes of water temperature. Nitrate supply from subsurface layers by seasonal vertical diffusion in autumn also helped to maintain the HABs. Vertical diffusion following MHWs in 2021 contributed to the long duration of the preferred temperature for K. selliformis and the occurrence of pre-bloom of K. selliformis, resulting in preconditioning and accelerating the HABs. However, simulations for normal years (i.e., the climatological mean during 2003–2018) showed that HABs could have occurred, even in the absence of MHWs. The simulations indicated that massive blooms of other phytoplankton species (e.g., diatoms) would not have occurred in 2021, even in the absence of a K. selliformis bloom. The implication was that the HABs in 2021 were the species-specific responses of K. selliformis. The proposed mechanism of the HABs was peculiar to our study area and differed from that previously reported for other K. selliformis blooms. Specifically, the preferred temperature for the HABs of K. selliformis was clearly lower than the previously reported preferred temperature of K. selliformis; thus, the physiological characteristics of the K. selliformis that bloomed in our study area differed from those of other K. selliformis strains. These discoveries provide the first evidence to explain how MHWs affect HABs, and to understand how inter-regional dissimilarities of K. selliformis can lead to large-scale, devastating outbreaks under different oceanographic conditions

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI- 74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60min after the intravenous injection of [18F]FAPI-74 (240631 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n 5 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P 5 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P 5 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P 5 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.This research was originally published in JNM. Tadashi Watabe, Sadahiro Naka, Mitsuaki Tatsumi et.al. Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions. J Nucl Med. 2023, 64(8), 1225-1231. © SNMMI

Circulating KCNH2 Current-Activating Factor in Patients with Heart Failure and Ventricular Tachyarrhythmia

It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF.We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia.Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF

Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives