J1406+0102: Dust Obscured Galaxy Hiding Super Eddington Accretion System with Bright Radio Emission

Recent high-$z$ quasar observations strongly indicate that super-Eddington accretion is a crucial phase to describe the existence of supermassive black holes (SMBHs) with $M_\mathrm{BH} \gtrsim 10^9 M_\odot$ at $z \gtrsim 7$. Motivated by the theoretical suggestion that the super-Eddington phase efficiently produces outflows and jets bright in radio bands, we search and find a super-Eddington radio-loud dust-obscured galaxy (DOG) J1406+0102 at $z=0.236$, through cross-matching of the infrared-bright DOGs of Noboriguchi et al. (2019) with the VLA/FIRST 1.4 GHz radio and the SDSS optical spectral catalog. DOG J1406+0102 shows broad components in the Balmer lines. Assuming those lines are from the broad line region, it gives BH mass estimation of $\log\ (M_\mathrm{BH}/M_\odot)=7.30 \pm 0.25$, and AGN luminosity of $\log (L_\mathrm{bol,[OIII]}/\mathrm{erg}~\mathrm{s}^{-1}) = 45.91\pm0.38$ estimated from the intrinsic [OIII] luminosity, resulting in super-Eddington accretion of $\lambda_\mathrm{Edd}\simeq 3$. We show that 1) DOG J1406+0102 is operating strong AGN feedback: the [OIII] outflow velocity exceeds the escape velocity of the host galaxy halo and the kinetic efficiency is obtained as $\approx$ 8% that can be sufficient to quench the host galaxy, 2) the expected future growth pathway of DOG J1406+0102 would join an over-massive BH trajectory and 3) radio-loud DOGs can provide a significant contribution to the high-energy ($\gtrsim$ 100 TeV) cosmic neutrino background if we assume DOG J1406+0102 as a representative of radio-loud DOGs.Comment: 10 pages, 5 figures, submitted to ApJ

Effects of insulin-like growth factor-1 on the mRNA expression of estradiol receptors, steroidogenic enzymes, and steroid production in bovine follicles

Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are synthesized through the actions of steroidogenic enzymes, specifically STAR, CYP11A1, HSD3B, and CYP19A1 in both theca cells (TCs) and granulosa cells (GCs), under the influence of gonadotropins. Particularly, estradiol 17 beta (E2) assumes a central role in follicular development and selection by activating estrogen receptors beta (ESR2) in GCs. We assessed ESR2 mRNA expression in GCs of developing follicles and investigated the impact of IGF-1 on the mRNA expression of ESR2, CYP19A1, FSHR, and LHCGR, STAR, CYP11A1, and HSD17B in cultured GCs and TCs, respectively. Additionally, we assessed the influence of IGF-1 on androstenedione (A4), progesterone (P4), and testosterone (T) production in TCs. Small-sized follicles (= 9 mm) (P < 0.05). IGF-1 increased the mRNA expression of ESR2, CYP19A1, and FSHR in GCs of follicles of both sizes, except for FSHR mRNA in medium-sized follicles (P < 0.05). IGF-1 significantly elevated mRNA expression of LHCGR, STAR, CYP11A1, and CYP17B in TCs of small-and medium-sized follicles (P < 0.05). Moreover, IGF-1 augmented the production of A4 and P4 but had no impact on T production in TCs of small-and medium-sized follicles. Taken together, our findings indicate that IGF-1 upregulates steroidogenic enzymes and steroid hormone production, underscoring the crucial role of IGF-1 in follicle development and selection

Effects of Early Sea-Ice Reduction on Zooplankton and Copepod Population Structure in the Northern Bering Sea During the Summers of 2017 and 2018

A remarkable early sea-ice reduction event was observed in the northern Bering Sea during 2018. In turn, this unusual hydrographic phenomenon affected several marine trophic levels, resulting in delayed phytoplankton blooms, phytoplankton community changes, and a northward shift of fish stocks. However, the response of the zooplankton community remains uncharacterized. Therefore, our study sought to investigate the zooplankton community shifts in the northern Bering Sea during the summers of 2017 and 2018 and evaluate the effects of early sea-ice melt events on the zooplankton community, population structure of large copepods, and copepod production. Five zooplankton communities were identified based on cluster analysis. Further, annual changes in the zooplankton community were identified in the Chirikov Basin. In 2017, the zooplankton community included abundant Pacific copepods transported by the Anadyr water. In 2018, however, the zooplankton community was dominated by small copepods and younger stages of large copepods (Calanus glacialis/marshallae and Metridia pacifica), which was likely caused by reproduction delays resulting from the early sea-ice reduction event. These environmental abnormalities increased copepod production; however, this higher zooplankton productivity did not efficiently reach the higher trophic levels. Taken together, our findings demonstrated that zooplankton community structure and production are highly sensitive to the environmental changes associated with early sea-ice reduction (e.g., warm temperatures and food availability)

The Effect of a Portable Electrical Muscle Stimulation Device at Home on Muscle Strength and Activation Patterns in Locomotive Syndrome Patients: A Randomized Control Trial

The aim of the present study was to quantify the effect of electrical muscle stimulation (EMS) intervention using a portable device on muscle strength and activation patterns in locomotive syndrome. Nineteen women were randomly assigned to the intervention group (n = 10; age = 71–82 years) and control group (n = 9; age = 70–84 years). Participants in the intervention group used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min/5 days/week). To understand the effects of EMS, the following measurements were made at baseline, 8 weeks, and 12 weeks: locomotive syndrome assessment score, knee extensor strength, vastus lateralis muscle activation patterns during a maximal isometric knee extension contraction using multi-channel surface electromyography, and muscle thickness. The locomotive syndrome assessment, muscle strength, muscle thickness, and muscle activity patterns in the intervention group were significantly different to control after 8 weeks (p \u3c 0.05). However, these results were not sustained at 12 weeks. EMS increased locomotor assessment scores, which were accompanied by enhanced muscle strength, increased muscle thickness, and changes in muscle activation patterns in locomotive syndrome patients. These results suggest that EMS is potentially useful for improving muscle neural activation and force output in locomotive syndrome

Stereoselective syntheses of (E)-α,β-didehydroamino acid and peptide containing its residue utilizing oxazolidinone derivative

金沢大学理工学域Reaction of methyl N-Boc-N-phenoxycarbonylglycinate with various aldehydes afforded the corresponding cis-4,5-oxazolidinone derivatives, which were effectively converted to (E)-α,β-didehydroamino acids by means of a base. Furthermore, N-deprotection of the oxazolidinone derivatives and subsequent coupling reaction with Boc-amino acid furnished the corresponding dipeptides, which were transformed to dipeptide containing α,β-didehydroamino acid with high E selectivity

Trauma airway management in emergency departments: a multicentre, prospective, observational study in Japan

Objectives: Although successful airway management is essential for emergency trauma care, comprehensive studies are limited. We sought to characterise current trauma care practice of airway management in the emergency departments (EDs) in Japan. Design: Analysis of data from a prospective, observational, multicentre registry—the Japanese Emergency Airway Network (JEAN) registry. Setting: 13 academic and community EDs from different geographic regions across Japan. Participants: 723 trauma patients who underwent emergency intubation from March 2010 through August 2012. Outcome measures ED characteristics, patient and operator demographics, methods of airway management, intubation success or failure at each attempt and adverse events. Results: A total of 723 trauma patients who underwent emergency intubation were eligible for the analysis. Traumatic cardiac arrest comprised 32.6% (95% CI 29.3% to 36.1%) of patients. Rapid sequence intubation (RSI) was the initial method chosen in 23.9% (95% CI 21.0% to 27.2%) of all trauma patients and in 35.5% (95% CI 31.4% to 39.9%) of patients without cardiac arrest. Overall, intubation was successful in ≤3 attempts in 96% of patients (95% CI 94.3% to 97.2%). There was a wide variation in the initial methods of intubation; RSI as the initial method was performed in 0–50.9% of all trauma patients among 12 EDs. Similarly, there was a wide variation in success rates and adverse event rates across the EDs. Success rates varied between 35.5% and 90.5% at the first attempt, and 85.1% and 100% within three attempts across the 12 EDs. Conclusions: In this multicentre prospective study in Japan, we observed a high overall success rate in airway management during trauma care. However, the methods of intubation and success rates were highly variable among hospitals

Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers. Since the majority of patients are diagnosed at an advanced stage, development of a detection method for PDAC at an earlier stage of disease progression is strongly desirable. Integrin αVβ6 is a promising target for early PDAC detection because its expression increases during precancerous changes. The present study aimed to develop an imaging probe for positron emission tomography (PET) which targets αVβ6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to αvβ6 integrin, as a probe scaffold, and 68Ga as a radioisotope. A20FMDV2 peptide has not been previously labeled with 68Ga. A cysteine residue was introduced to the N-terminus of the probe at a site-specific conjugation of maleimide-NOTA (mal-NOTA) chelate. Different numbers of glycine residues were also introduced between cysteine and the A20FMDV2 sequence as a spacer in order to reduce the steric hindrance of the mal-NOTA on the binding probe to αVβ6 integrin. In vitro, the competitive binding assay revealed that probes containing a 6-glycine linker ([natGa]CG6 and [natGa]Ac-CG6) showed high affinity to αVβ6 integrin. Both probes could be labeled by 67/68Ga with high radiochemical yield (>50%) and purity (>98%). On biodistribution analysis, [67Ga]Ac-CG6 showed higher tumor accumulation, faster blood clearance, and lower accumulation in the surrounding organs of pancreas than did [67Ga]CG6. The αVβ6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the αVβ6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of αVβ6 integrin in PDAC

Impact of renal insufficiency on long-term clinical outcome in patients with heart failure treated by cardiac resynchronization therapy

AbstractBackgroundRenal insufficiency is recognized as a predictor of mortality and adverse outcome in heart failure (HF) patients. However, the long-term clinical outcome of cardiac resynchronization therapy (CRT) in Japanese HF patients with renal insufficiency remains uncertain.MethodsWe evaluated 67 consecutive patients who underwent CRT at our hospital. The patients were divided into two groups according to a baseline estimated glomerular filtration rate (e-GFR) cut-off value of 50ml/min, which is defined as the time at which patients should be referred to a nephrologist, by the Japanese Society of Nephrology. Follow-up echocardiographic findings and renal function were examined at 3–6 months after CRT. Then, we compared long-term clinical outcomes between the two groups, and analyzed the effect of CRT on renal function, echocardiographic parameters and cardiac survival.ResultsDuring a mean follow-up period of 30.3 months, patients with advanced renal insufficiency (e-GFR<50ml/min) had significant higher all-cause mortality (log-rank p=0.033) and higher cardiac mortality combined with HF hospitalization (log-rank p=0.017) than patients with e-GFR≥50ml/min. Multivariate analysis revealed that advanced renal insufficiency was an independent predictor of cardiac mortality combined with HF hospitalization (odds ratio=3.01, p=0.008). Subgroup analysis in the baseline advanced renal insufficiency group revealed that patients with preserved renal function by CRT (<10% reduction in e-GFR) had a higher rate of decrease of left ventricular end-systolic diameter (−14.0% vs. −0.8%, p=0.023) and lower cardiac mortality combined with HF hospitalization (log-rank p=0.029) compared with patients with deterioration of renal function (≥10% reduction in e-GFR).ConclusionsThe present study suggests that advanced renal insufficiency is quite useful for the prediction of worsening clinical outcomes in HF patients treated by CRT. Preservation of renal function by CRT brings about better cardiac survival through prevention of adverse cardiac events, even in HF patients with advanced renal insufficiency

Notable underlying mechanism for pancreatic β-cell dysfunction and atherosclerosis: Pleiotropic roles of incretin and insulin signaling

Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state, expression levels of insulin gene transcription factors and incretin receptors are downregulated, which we think is closely associated with β-cell failure. These data also suggest that it would be better to use incretin-based drugs at an early stage of diabetes when incretin receptor expression is preserved. Indeed, it was shown that incretin-based drugs exerted more protective effects on β-cells at an early stage. Furthermore, it was shown recently that endothelial cell dysfunction was also associated with pancreatic β-cell dysfunction. After ablation of insulin signaling in endothelial cells, the β-cell function and mass were substantially reduced, which was also accompanied by reduced expression of insulin gene transcription factors and incretin receptors in β-cells. On the other hand, it has been drawing much attention that incretin plays a protective role against the development of atherosclerosis. Many basic and clinical data have underscored the importance of incretin in arteries. Furthermore, it was shown recently that incretin receptor expression was downregulated in arteries under diabetic conditions, which likely diminishes the protective effects of incretin against atherosclerosis. Furthermore, a series of large-scale clinical trials (SPAED-A, SPIKE, LEADER, SUSTAIN-6, REWIND, PIONEER trials) have shown that various incretin-related drugs have beneficial effects against atherosclerosis and subsequent cardiovascular events. These data strengthen the hypothesis that incretin plays an important role in the arteries of humans, as well as rodents.Kaneto, H.; Obata, A.; Kimura, T.; Shimoda, M.; Sanada, J.; Fushimi, Y.; Katakami, N.; Matsuoka, T.; Kaku, K. Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling. Int. J. Mol. Sci. 2020, 21, 9444

Cognitive clustering in schizophrenia patients, their first-degree relatives and healthy subjects is associated with anterior cingulate cortex volume

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ