Observation of superfluidity in two- and one-dimensions

Even though there is no long-range-ordered state of a superfluid in dimensions lower than the three-dimension (3D) such as bulk ⁴He liquid, superfluidity has been observed for flat ⁴He films in 2D and recently for nanotubes of ⁴He in 1D by the torsional oscillator method. In the 2D state, in addition to the superfluid below the 2D Kosterlitz–Thouless transition temperature TKT, superfluidity is also observed in a normal fluid state above TKT, which depends strongly on the measurement frequency and the system size. In the 1D state of the nano-tubes, superfluidity is directly observed as a frequency shift in the torsional oscillator experiment. Some calcula-tions suggest a superfluidity of a 1D Bose fluid with a finite length, where thermal excitations of 2-phase winding play the main role for superfluid onset of each tube. Dynamics of the 1D superfluidity is also suggested by observing the dissipation in the torsional oscillator experiment

Deletion of Long Isoform of Eukaryotic Elongation Factor 1Bδ Leads to Audiogenic Seizures and Aversive Stimulus-Induced Long-Lasting Activity Suppression in Mice

Alternative splicing enables a gene to give rise to diverse protein products. The Eef1d gene produces two isoforms: a short isoform that encodes translation elongation factor 1Bδ (eEF1Bδ1), and a long isoform that encodes the heat shock-responsive transcription factor eEF1BδL. Previously, we found that eEF1BδL was a splice variant that was specific to the brain and testis, and the protein encoded is thought to have a function in the central nervous system. In this study, we generated knockout (KO) mice of C57BL/6J background that selectively lacked a specific exon in Eef1d for the long isoform. These KO mice lacked eEF1BδL, but not eEF1Bδ1, in the brain. Although the KO mice showed normal anxiety-related and learning behavior in behavioral tests, some showed severe seizures in response to loud sounds (90 dBA), an audiogenic seizures (AGS) response. Furthermore, after the KO mice had been subjected to the fear conditioning test, they showed remarkably decreased locomotor activity in their home cage and in the open-field and elevated plus-maze tests. After the fear conditioning test, a significant decrease in brain weight, atrophy of the hippocampus and midbrain, and reduced cortical layer thickness were observed in the KO mice. We also found a compensatory increase in the eEF1Bδ1 level and elevated protein synthesis with the induction of endoplasmic reticulum stress markers in these mice. Our results suggest that eEF1BδL has an important role in normal brain function especially when exposed to external stimuli

CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology

Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types

Submillimeter ALMA Observations of the Dense Gas in the Low-Luminosity Type-1 Active Nucleus of NGC 1097

We present the first 100 pc scale view of the dense molecular gas in the central ~ 1.3 kpc region of the type-1 Seyfert NGC 1097 traced by HCN (J=4-3) and HCO+ (J=4-3) lines afforded with ALMA band 7. This galaxy shows significant HCN enhancement with respect to HCO+ and CO in the low-J transitions, which seems to be a common characteristic in AGN environments. Using the ALMA data, we study the characteristics of the dense gas around this AGN and search for the mechanism of HCN enhancement. We find a high HCN (J=4-3) to HCO+ (J=4-3) line ratio in the nucleus. The upper limit of the brightness temperature ratio of HCN (v2=1^{1f}, J=4-3) to HCN (J=4-3) is 0.08, which indicates that IR pumping does not significantly affect the pure rotational population in this nucleus. We also find a higher HCN (J=4-3) to CS (J=7-6) line ratio in NGC 1097 than in starburst galaxies, which is more than 12.7 on the brightness temperature scale. Combined from similar observations from other galaxies, we tentatively suggest that this ratio appears to be higher in AGN-host galaxies than in pure starburst ones similar to the widely used HCN to HCO+ ratio. LTE and non-LTE modeling of the observed HCN and HCO+ lines using J=4-3 and 1-0 data from ALMA, and J=3-2 data from SMA, reveals a high HCN to HCO+ abundance ratio (5 < [HCN]/[HCO+] < 20: non-LTE analysis) in the nucleus, and that the high-J lines (J=4-3 and 3-2) are emitted from dense (10^{4.5} < n_H2 [/cc] < 10^6), hot (70 < Tkin [K] < 550) regions. Finally we propose that the high temperature chemistry is more plausible to explain the observed enhanced HCN emission in NGC 1097 than the pure gas phase PDR/XDR chemistry.Comment: 28 pages, 17 figures, 10 tables. Accepted to PAS

ALMA Observations of the Submillimeter Dense Molecular Gas Tracers in the Luminous Type-1 Active Nucleus of NGC 7469

We present ALMA Cycle 1 observations of the central kpc region of the luminous type-1 Seyfert galaxy NGC 7469 with unprecedented high resolution (0.5$"$ $\times$ 0.4$"$ = 165 pc $\times$ 132 pc) at submillimeter wavelengths. Utilizing the wide-bandwidth of ALMA, we simultaneously obtained HCN(4-3), HCO$^+$(4-3), CS(7-6), and partially CO(3-2) line maps, as well as the 860 $\mu$m continuum. The region consists of the central $\sim$ 1$"$ component and the surrounding starburst ring with a radius of $\sim$ 1.5$"$-2.5$"$. Several structures connect these components. Except for CO(3-2), these dense gas tracers are significantly concentrated towards the central $\sim$ 1$"$, suggesting their suitability to probe the nuclear regions of galaxies. Their spatial distribution resembles well those of centimeter and mid-infrared continuum emissions, but it is anti-correlated with the optical one, indicating the existence of dust obscured star formation. The integrated intensity ratios of HCN(4-3)/HCO$^+$(4-3) and HCN(4-3)/CS(7-6) are higher at the AGN position than at the starburst ring, which is consistent to our previous findings (submm-HCN enhancement). However, the HCN(4-3)/HCO$^+$(4-3) ratio at the AGN position of NGC 7469 (1.11$\pm$0.06) is almost half of the corresponding value of the low-luminosity type-1 Seyfert galaxy NGC 1097 (2.0$\pm$0.2), despite the more than two orders of magnitude higher X-ray luminosity of NGC 7469. But the ratio is comparable to that of the close vicinity of the AGN of NGC 1068 ($\sim$ 1.5). Based on these results, we speculate that some other heating mechanisms than X-ray (e.g., mechanical heating due to AGN jet) can contribute significantly for shaping the chemical composition in NGC 1097.Comment: Fixed typos in the title. 15 pages, 8 figures, 4 tables: accepted for publication in ApJ. Comments welcom

Killer immunoglobulin-like receptor genotype did not correlate with response to anti-PD-1 antibody treatment in a Japanese cohort

Immune checkpoint blockade (ICB) induces a remarkable response in patients with certain cancers. However, the response rate is not yet satisfactory. Biomarkers that help physicians identify patients who would benefit from ICB need to be developed. Killer immunoglobulin-like receptors (KIRs) are a class of receptors that are mainly expressed by natural killer cells. KIR genotypes have been shown to influence the outcomes of patients with neuroblastoma and hematopoietic malignancies. KIRs may thus influence the clinical outcomes of melanoma patients receiving nivolumab. We aimed to identify the KIR genotype, or KIR/KIR-ligand combinations, which influence the outcomes of melanoma patients receiving nivolumab. We genotyped 112 melanoma patients who were treated with nivolumab for KIR and human leukocyte antigen. The clinical records of the patients were analyzed to determine if they showed a response to nivolumab, and whether or not they experienced adverse events. Our analysis showed that no KIR gene was associated with a response to nivolumab. The KIR/KIR-ligand combination did not correlate with a response to nivolumab. KIR genes were not predictive of experiencing adverse events of grade 2 or greater. We conclude that the KIR genotype or KIR/KIR-ligand genotype do not show predictive value in melanoma patients receiving nivolumab

Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations

金沢大学医薬保健学総合研究科先進的地域医療研究講座 = Department of Advanced Research in Community MedicineTo clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions’ clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect

Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy