bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and reliability of the Palliative Care Transition Measure for Caregivers (PCTM-C)
Authors: D'Angelo Daniela , Mastroianni Chiara , Artico Marco , Biagioli Valentina , Latina Roberto , Guarda Michela , Piredda Michela , De Marinis Maria Grazia
Published: January 2018

Objective

Patients suffering from advanced disease face different care transitions. The transition from acute to palliative care is challenging and may lead to the discontinuity of care. Family caregivers become important sources of information, as patients begin to experience difficulties in coping with emotional transition events. The Care Transition Measure was developed to evaluate care transitions as experienced by the elderly. It has never been used in palliative care. The aim of this study was to test the validity and reliability of a modified version of the Palliative Care Transition Measure, specifically the Palliative Care Transition Measure for Caregivers (PCTM-C).

Method

The study included two main phases. Phase I focused on the construction of a modified version of the Palliative Care Transition Measure through two focus groups and by computing the content validity index. Phase II focused on testing the psychometric properties of the PCTM-C on 272 family caregivers through confirmatory factor analysis.

Result

The content validity index for each of the items was higher than 0.80, whereas that for the scale was 0.95. The model tested with confirmatory factor analysis fitted the data well and confirmed that the transition measures referred to communication, integrated care and a trusting-relationship, and therefore the core dimensions of continuity according to existing conceptual models. The internal consistency was high (Cronbach's alpha = 0.94).

Significance of results

The PCTM-C proved to be a suitable measure of the quality of such transitions. It may be used in clinical practice as a continuity quality indicator and has the potential to guide interventions to enhance family caregivers’ experience of care continuity.
The impact of slow economic growth on health sector reform: a cross-national perspective
Authors: Saltman Richard B.
Published: January 2018

This paper assesses recent health sector reform strategies across Europe adopted since the onset of the 2008 financial crisis. It begins with a brief overview of the continued economic pressure on public funding for health care services, particularly in tax-funded Northern European health care systems. While economic growth rates across Europe have risen a bit in the last year, they remain below the level necessary to provide the needed expansion of public health sector revenues. This continued public revenue shortage has become the central challenge that policymakers in these health systems confront, and increasingly constrains their potential range of policy options. The paper then examines the types of targeted reforms that various European governments have introduced in response to this increased fiscal stringency. Particularly in tax-funded health systems, these efforts have been focused on two types of changes on the production side of their health systems: consolidating and/or centralizing administrative authority over public hospitals, and revamping secondary and primary health services as well as social services to reduce the volume, cost and less-than-optimal outcomes of existing public elderly care programs. While revamping elderly care services also was pursued in the social health insurance (SHI) system in the Netherlands, both the Dutch and the German health systems also made important changes on the financing side of their health systems. Both types of targeted reforms are illustrated through short country case studies. Each of these country assessments flags up new mechanisms that have been introduced and which potentially could be reshaped and applied in other national health sector contexts. Reflecting the tax-funded structure of the Canadian health system, the preponderance of cases discussed focus on tax-funded countries (Norway, Denmark, Sweden, Finland, England, Ireland), with additional brief assessments of recent changes in the SHI-funded health systems in the Netherlands and Germany. The paper concludes that post-2008 European reforms have helped stretch existing public funds more effectively, but seem unlikely to resolve the core problem of inadequate overall public funding, particularly in tax-based health systems. This observation suggests that ongoing Canadian efforts to consolidate and better integrate its health care providers, while important, may not eliminate long-term health sector-funding dilemmas.
The efficacy of life insurance company general account equity asset allocations: a safety-first perspective using vine copulas
Authors: Timmer Ryan , Broussard John Paul , Booth G. Geoffrey
Published: January 2018

We study the asset allocation decision of a life insurance company’s general account with respect to the possibility of large negative economic shocks and examine how this account is affected by policyholder investment decisions in the company’s separate account. This is accomplished using a performance metric that incorporates downside risk measured using univariate and multivariate extreme value distributions. Because of its well-known price volatility, diversification attributes, and significant weight in the combined general and separate accounts, our primary focus is the company’s equity investments. Although industry asset allocations have varied over the past two decades, we find that the actual allocations to equity in the general account are close to the allocation percentages suggested by our extreme value metrics and both are far below the maximum values indicated by the relevant regulatory bodies.
Assessment of New Herbicide Programs for Cowpea Production
Authors: Rouse Christopher E. , Roma-Burgos Nilda , Estorninos Leopoldo E. , Penka Teal M.
Published: January 2018

Cowpea is a major specialty crop in the southern US. In recent years, no new herbicide programs have been evaluated for cowpea despite additional herbicide registrations. Studies were conducted from 2014 to 2016 at Fayetteville and Kibler, Arkansas to assess new herbicide programs for cowpea production. The herbicide programs included: three commercial standard programs; fomesafen (PPL, 0.21 kgha−1)-, flumioxazin (PPL, 0.21 kgha−1)-, and halosulfuron (PPL, 0.054 kgha−1)-based programs with or withoutS-metolachlor (1.12 kgha−1) fb imazethapyr (0.07 kgha−1); and two sets of sulfentrazone (PPL/PRE)-based programs applied alone (0.21 kgha−1) or as a pre-mixture with carfentrazone (0.11 kgha−1+0.01 kgha−1) with or withoutS-metolachlor (1.12 kgha−1). The sulfentrazone-based programs included POST applications of imazethapyr fb sethoxydim (0.32 kgha−1) or fluthiacet-methyl (0.0067 kgha−1) and sethoxydim as necessary. In 2014 and 2015, crop stand loss was minimal and crop injury was generally low (<20%). Weed control from sulfentrazone- and flumioxazin-based programs was excellent (>90%). In 2016, with heavy rainfall around planting time, sulfentrazone-containing programs reduced cowpea yield 45% to 60%. Flumioxazin-based programs caused >85% injury at Kibler early-season, which lasted until harvest. Heavy rainfall also reduced efficacy of residual herbicides. In general, the sulfentrazone- and flumioxazin-based treatments consistently yielded similar to the weed-free controls. The majority of the programs had <60% weed control in Fayetteville early in the season. POST herbicides improved weed control to >90% in most treatments. Palmer amaranth and annual grass control was generally better in Kibler, with >80% control at harvest. Sulfentrazone is registered for cowpea and is effective on Palmer amaranth, but growers need to be careful about where and when to use it. Flumioxazin should be considered for registration in cowpea once its use pattern and location-specific recommendations are well defined.
Living apart together—bacterial volatiles influence methanotrophic growth and activity
Authors: Veraart A J , Garbeva P , van Beersum F , Ho A , Hordijk C A , Meima-Franke M , Zweers A J , Bodelier P L E
Published: January 2018

Volatile organic compounds play an important role in microbial interactions. However, little is known about how volatile-mediated interactions modulate biogeochemical processes. In this study, we show the effect of volatile-mediated interaction on growth and functioning of aerobic methane-oxidizing bacteria, grown in co-culture with five different heterotrophs. Both growth and methane oxidation of Methylobacter luteus were stimulated by interaction with specific heterotrophs. In Methylocystis parvus, we observed significant growth promotion, while methane oxidation was inhibited. Volatolomics of the interaction of each of the methanotrophs with Pseudomonas mandelii, revealed presence of a complex blend of volatiles, including dimethylsulfide, dimethyldisulfide, and bicyclic sesquiterpenes. Although the ecological role of the detected compounds remains to be elucidated, our results provide unprecedented insights into interspecific relations and associated volatiles for stimulating methanotroph functioning, which is of substantial environmental and biotechnological significance.
Multifunctional viral protein γ34.5 manipulates nucleolar protein NOP53 for optimal viral replication of HSV-1
Authors: Meng Wen , Han Shi-Chong , Li Cui-Cui , Dong Hui-Jun , Wang Xiao-Jia
Published: January 2018

To ensure efficient virus replication, herpes simplex virus type 1 (HSV-1) encodes several viral proteins to counter host defense response upon infection. Among these proteins, the multifunctional viral protein γ34.5 crucially interferes with or disrupts several antiviral pathways at multiple levels. The current study shows that γ34.5 utilizes nucleolar protein NOP53 to facilitate the dephosphorylation of eukaryotic initiation factor eIF2α for efficient viral translation. Our study shows that: (1) ectopic expression of NOP53 greatly increases the intracellular and extracellular viral yields of HSV-1 (wild strain F) in type I interferon-deficient Vero cells, and more subtly promotes viral replication of γ34.5 deletion mutant virus HSV-1/Δγ34.5. (2) NOP53 is migrated from nuclei in HSV-1/F infected cells, but is redistributed incompletely after infection by either HSV-1/Δγ34.5 or ICP4 deletion mutant virus HSV-1/d120 (replication inadequate). Ectopic expression of γ34.5, consequently, induces cytoplasmic translocation of NOP53 in response to HSV-1/Δγ34.5 infection. (3) Increase of NOP53, in two forms of transient transfection and in vitro expression, attenuates the phosphorylation level of eIF2α in HSV-1/F infected cells, but fails to affect eIF2α phosphorylation induced by HSV-1/Δγ34.5 infection. (4) Knockdown of NOP53, which impairs the specific interaction between γ34.5 and protein phosphatase PP1α, disrupts the ability of γ34.5 to maintain HSV-1 virulence. (5) NOP53 knockdown also significantly reduces tissue damage and decreases viral yield in livers of HSV-1 infected mice. Our findings expand the understanding of the underlying mechanism by which viral protein γ34.5 induces NOP53 redistribution; cytoplasmic NOP53 facilitates γ34.5 recruitment of PP1α to dephosphorylate eIF2α, for optimal viral replication. This paper also demonstrates that blocking the specific interaction between γ34.5 and PP1α would be a useful approach for the development of antiviral agents.
Rosmarinic acid attenuates cardiac fibrosis following long-term pressure overload via AMPKα/Smad3 signaling
Authors: Zhang Xin , Ma Zhen-Guo , Yuan Yu-Pei , Xu Si-Chi , Wei Wen-Ying , Song Peng , Kong Chun-Yan , Deng Wei , Tang Qi-Zhu
Published: January 2018

Agonists of peroxisome proliferator-activated receptor gamma (PPAR-γ) can activate 5′ AMP-activated protein kinase alpha (AMPKα) and exert cardioprotective effects. A previous study has demonstrated that rosmarinic acid (RA) can activate PPAR-γ, but its effect on cardiac remodeling remains largely unknown. Our study aimed to investigate the effect of RA on cardiac remodeling and to clarify the underlying mechanism. Mice were subjected to aortic banding to generate pressure overload induced cardiac remodeling and then were orally administered RA (100 mg/kg/day) for 7 weeks beginning 1 week after surgery. The morphological examination, echocardiography, and molecular markers were used to evaluate the effects of RA. To ascertain whether the beneficial effect of RA on cardiac fibrosis was mediated by AMPKα, AMPKα2 knockout mice were used. Neonatal rat cardiomyocytes and fibroblasts were separated and cultured to validate the protective effect of RA in vitro. RA-treated mice exhibited a similar hypertrophic response as mice without RA treatment, but had an attenuated fibrotic response and improved cardiac function after pressure overload. Activated AMPKα was essential for the anti-fibrotic effect of RA via inhibiting the phosphorylation and nuclear translocation of Smad3 in vivo and in vitro, and AMPKα deficiency abolished RA-mediated protective effects. Small interfering RNA against Ppar-γ (siPpar-γ) and GW9662, a specific antagonist of PPAR-γ, abolished RA-mediated AMPKα phosphorylation and alleviation of fibrotic response in vitro. RA attenuated cardiac fibrosis following long-term pressure overload via AMPKα/Smad3 signaling and PPAR-γ was required for the activation of AMPKα. RA might be a promising therapeutic agent against cardiac fibrosis.
Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease
Authors: Sartini Alessandro , Gitto Stefano , Bianchini Marcello , Verga Maria Chiara , Di Girolamo Maria , Bertani Angela , Del Buono Mariagrazia , Schepis Filippo , Lei Barbara , De Maria Nicola , Villa Erica
Published: January 2018

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6–84), surgery for IBD (OR 15.1, 95% CI 3.1–73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4–110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0–0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.
Optineurin-mediated mitophagy protects renal tubular epithelial cells against accelerated senescence in diabetic nephropathy
Authors: Chen Kehong , Dai Huanzi , Yuan Junjie , Chen Jia , Lin Lirong , Zhang Weiwei , Wang Limin , Zhang Jianguo , Li Kailong , He Yani
Published: January 2018

Premature senescence is a key process in the progression of diabetic nephropathy (DN). Premature senescence of renal tubular epithelial cells (RTEC) in DN may result from the accumulation of damaged mitochondria. Mitophagy is the principal process that eliminates damaged mitochondria through PTEN-induced putative kinase 1 (PINK1)-mediated recruitment of optineurin (OPTN) to mitochondria. We aimed to examine the involvement of OPTN in mitophagy regulation of cellular senescence in RTEC in the context of DN. In vitro, the expression of senescence markers P16, P21, DcR2, SA-β-gal, SAHF, and insufficient mitophagic degradation marker (mitochondrial P62) in mouse RTECs increased after culture in 30 mM high-glucose (HG) conditions for 48 h. Mitochondrial fission/mitophagy inhibitor Mdivi-1 significantly enhanced RTEC senescence under HG conditions, whereas autophagy/mitophagy agonist Torin1 inhibited cell senescence. MitoTempo inhibited HG-induced mitochondrial reactive oxygen species and cell senescence with or without Mdivi-1. The expression of PINK1 and OPTN, two regulatory factors for mitophagosome formation, decreased significantly after HG stimulation. Overexpression of PINK1 did not enhance mitophagosome formation under HG conditions. OPTN silencing significantly inhibited HG-induced mitophagosome formation, and overexpression of OPTN relieved cellular senescence through promoting mitophagy. In clinical specimens, renal OPTN expression was gradually decreased with increased tubulointerstitial injury scores. OPTN-positive renal tubular cells did not express senescence marker P16. OPTN expression also negatively correlated with serum creatinine levels, and positively correlated with eGFR. Thus, OPTN-mediated mitophagy plays a crucial regulatory role in HG-induced RTEC senescence in DN. OPTN may, therefore, be a potential antisenescence factor in DN.
Long non-coding RNA and microRNA-675/let-7a mediates the protective effect of melatonin against early brain injury after subarachnoid hemorrhage via targeting TP53 and neural growth factor
Authors: Yang Song , Tang Wanzhong , He Yuchao , Wen Linbao , Sun Bin , Li Shengli
Published: January 2018

The objective of this study was to identify the protective effect of melatonin (MT) against early brain injury (EBI) following subarachnoid hemorrhage (SAH) and explore the underlying molecular mechanism. Real-time polymerase chain reaction (PCR) and luciferase assay were utilized to detect the effect of MT on H19 expression level, computation analysis and luciferase assay were conducted to the underlying mechanism of let-7a and miR-675. Real-time PCR, western blot analysis, immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry analysis were performed to detect the effect of MT on H19, miR-675, let-7a, TP53, neural growth factor (NGF) levels, cell viability, and apoptosis status. Melatonin increased H19 expression level by enhancing H19 transcriptional efficiency in a concentration-dependent manner. MiR-675 and let-7a directly targeted P53 and NGF, respectively, and miR-675 reduced luciferase activity of wild-type but not mutant TP53 3′UTR. Meanwhile, let-7a suppressed luciferase activity of wild-type but not mutant NGF 3′UTR. H2O2 increased number of SA-b-gal, and while MT administration repressed the premature senescence. H2O2 obviously upregulated expressions of H19, miR-675, and NGF, and downregulated let-7a and TP53 levels; however, MT treatment reduced expressions of H19, miR-675, and NGF, and improved let-7a and TP53 levels. Treating with MT attenuated the neurological deficits and reduced the brain swelling. MT treatment repressed apoptosis of neurons caused by SAH. Levels of H19, miR-675, and NGF were much higher in the SAH +  MT group, while there were even higher levels of H19, miR-675, and NGF in the SAH group than in the sham group; levels of let-7a and TP53 were much lower in the SAH + MT group, while they were even lower in the SAH group than in the sham group. Our study revealed that treatment with MT protected against EBI after SAH by modulating the signaling pathways of H19-miR-675-P53-apoptosis and H19-let-7a-NGF-apoptosis.
MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6
Authors: Dang Yujie , Wang Xiaoyan , Hao Yajing , Zhang Xinyue , Zhao Shidou , Ma Jinlong , Qin Yingying , Chen Zi-Jiang
Published: January 2018

Premature ovarian insufficiency (POI) imposes great challenges on women’s fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively. MiR-379-5p, PARP1, and XRCC6 were differentially expressed in GCs of bPOI as revealed by microarrays. Subsequently, functional studies demonstrated that miR-379-5p overexpression inhibited granulosa cell proliferation and attenuated DNA repair efficiency. Furthermore, both PARP1 and XRCC6 showed lower levels in GCs from patients with bPOI and were identified as executives of miR-379-5p. Therefore, our data first uncovered potentially pathogenic miR-379-5p and two novel targets PARP1 and XRCC6 in bPOI, which corroborated the significance of DNA repair for POI, and brought up an epigenetic explanation for the disease.
Structure-guided design of an Hsp90β N-terminal isoform-selective inhibitor
Authors: Khandelwal Anuj , Kent Caitlin N. , Balch Maurie , Peng Shuxia , Mishra Sanket J. , Deng Junpeng , Day Victor W. , Liu Weiya , Subramanian Chitra , Cohen Mark , Holzbeierlein Jeffery M. , Matts Robert , Blagg Brian S. J.
Published: January 2018

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors of Hsp90 have entered clinical trials, all of which bind the Hsp90 N-terminus and exhibit pan-inhibitory activity against all four Hsp90 isoforms. pan-Inhibition of Hsp90 appears to be detrimental as toxicities have been reported alongside induction of the pro-survival heat shock response. The development of Hsp90 isoform-selective inhibitors represents an alternative approach towards the treatment of cancer that may limit some of the detriments. Described herein is a structure-based approach to design isoform-selective inhibitors of Hsp90β, which induces the degradation of select Hsp90 clients without concomitant induction of Hsp90 levels. Together, these initial studies support the development of Hsp90β-selective inhibitors as a method to overcome the detriments associated with pan-inhibition.
A carbon nanotube tape for serial-section electron microscopy of brain ultrastructure
Authors: Kubota Yoshiyuki , Sohn Jaerin , Hatada Sayuri , Schurr Meike , Straehle Jakob , Gour Anjali , Neujahr Ralph , Miki Takafumi , Mikula Shawn , Kawaguchi Yasuo
Published: January 2018

Automated tape-collecting ultramicrotomy in conjunction with scanning electron microscopy (SEM) is a powerful approach for volume electron microscopy and three-dimensional neuronal circuit analysis. Current tapes are limited by section wrinkle formation, surface scratches and sample charging during imaging. Here we show that a plasma-hydrophilized carbon nanotube (CNT)-coated polyethylene terephthalate (PET) tape effectively resolves these issues and produces SEM images of comparable quality to those from transmission electron microscopy. CNT tape can withstand multiple rounds of imaging, offer low surface resistance across the entire tape length and generate no wrinkles during the collection of ultrathin sections. When combined with an enhanced en bloc staining protocol, CNT tape-processed brain sections reveal detailed synaptic ultrastructure. In addition, CNT tape is compatible with post-embedding immunostaining for light and electron microscopy. We conclude that CNT tape can enable high-resolution volume electron microscopy for brain ultrastructure analysis.
Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology
Authors: Fujita Kyota , Chen Xigui , Homma Hidenori , Tagawa Kazuhiko , Amano Mutsuki , Saito Ayumu , Imoto Seiya , Akatsu Hiroyasu , Hashizume Yoshio , Kaibuchi Kozo , Miyano Satoru , Okazawa Hitoshi
Published: January 2018

Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI). Phosphoproteomic analysis of this model revealed activation of signaling pathways connecting PKC and MAPK to tau prior to TDP43 aggregation and cognitive impairments, and identified PKCα as the kinase responsible for the early-stage tau phosphorylation at Ser203. Disinhibition of Gas6 binding to Tyro3 due to PGRN reduction results in activation of PKCα via PLCγ, inducing tau phosphorylation at Ser203, mislocalization of tau to dendritic spines, and spine loss. Administration of a PKC inhibitor, B-Raf inhibitor, or knockdown of molecules in the Gas6-Tyro3-tau axis rescues spine loss and cognitive impairment of PGRN-KI mice. Collectively, these results suggest that targeting of early-stage and aggregation-independent tau signaling represents a promising therapeutic strategy for this disease.
Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors
Authors: Wang Runming , Lai Tsz-Pui , Gao Peng , Zhang Hongmin , Ho Pak-Leung , Woo Patrick Chiu-Yat , Ma Guixing , Kao Richard Yi-Tsun , Li Hongyan , Sun Hongzhe
Published: January 2018

Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.
A peak in the critical current for quantum critical superconductors
Authors: Jung Soon-Gil , Seo Soonbeom , Lee Sangyun , Bauer Eric D. , Lee Han-Oh , Park Tuson
Published: January 2018

Generally, studies of the critical current Ic are necessary if superconductors are to be of practical use, because Ic sets the current limit below which there is a zero-resistance state. Here, we report a peak in the pressure dependence of the zero-field Ic, Ic(0), at a hidden quantum critical point (QCP), where a continuous antiferromagnetic transition temperature is suppressed by pressure toward 0 K in CeRhIn5 and 4.4% Sn-doped CeRhIn5. The Ic(0)s of these Ce-based compounds under pressure exhibit a universal temperature dependence, underlining that the peak in zero-field Ic(P) is determined predominantly by critical fluctuations associated with the hidden QCP. The dc conductivity σdc is a minimum at the QCP, showing anti-correlation with Ic(0). These discoveries demonstrate that a quantum critical point hidden inside the superconducting phase in strongly correlated materials can be exposed by the zero-field Ic, therefore providing a direct link between a QCP and unconventional superconductivity.
The SR protein B52/SRp55 regulates splicing of the period thermosensitive intron and mid-day siesta in Drosophila
Authors: Zhang Zhichao , Cao Weihuan , Edery Isaac
Published: January 2018

Similar to many diurnal animals, Drosophila melanogaster exhibits a mid-day siesta that is more robust as temperature increases, an adaptive response that aims to minimize the deleterious effects from exposure to heat. This temperature-dependent plasticity in mid-day sleep levels is partly based on the thermal sensitive splicing of an intron in the 3′ untranslated region (UTR) of the circadian clock gene termed period (per). In this study, we evaluated a possible role for the serine/arginine-rich (SR) splicing factors in the regulation of dmpi8 splicing efficiency and mid-day siesta. Using a Drosophila cell culture assay we show that B52/SRp55 increases dmpi8 splicing efficiency, whereas other SR proteins have little to no effect. The magnitude of the stimulatory effect of B52 on dmpi8 splicing efficiency is modulated by natural variation in single nucleotide polymorphisms (SNPs) in the per 3′ UTR that correlate with B52 binding levels. Down-regulating B52 expression in clock neurons increases mid-day siesta and reduces dmpi8 splicing efficiency. Our results establish a novel role for SR proteins in sleep and suggest that polymorphisms in the per 3′ UTR contribute to natural variation in sleep behavior by modulating the binding efficiencies of SR proteins.
Design of an acoustic superlens using single-phase metamaterials with a star-shaped lattice structure
Authors: Chen Meng , Jiang Heng , Zhang Han , Li Dongsheng , Wang Yuren
Published: January 2018

We propose a single-phase super lens with a low density that can achieve focusing of sound beyond the diffraction limit. The super lens has a star-shaped lattice structure made of steel that offers abundant resonances to produce abnormal dispersive effects as determined by negative parameter indices. Our analysis of the metamaterial band structure suggests that these star-shaped metamaterials have double-negative index properties, that can mediate these effects for sound in water. Simulations verify the effective focusing of sound by a single-phase solid lens with a spatial resolution of approximately 0.39 λ. This superlens has a simple structure, low density and solid nature, which makes it more practical for application in water-based environments.
Identification of OsGGR2, a second geranylgeranyl reductase involved in α-tocopherol synthesis in rice
Authors: Kimura Eiichi , Abe Takumi , Murata Kazumasa , Kimura Toshiyuki , Otoki Yurika , Yoshida Taiji , Miyazawa Teruo , Nakagawa Kiyotaka
Published: January 2018

Tocopherol (Toc) and tocotrienol (T3) are abundant in rice bran. Geranylgeranyl reductase (GGR) is an essential enzyme for Toc production that catalyzes the reduction of geranylgeranyl pyrophosphate and geranylgeranyl-chlorophyll. However, we found that a rice mutant line with inactivated Os02g0744900 (OsGGR1/LYL1/OsChl P) gene produces Toc, suggesting that rice plants may carry another enzyme with GGR activity. Using an RNA-mediated interference technique, we demonstrated that the Os01g0265000 (“OsGGR2”) gene product has GGR activity. This result supports the existence of two GGR genes (OsGGR1 and OsGGR2) in rice, in contrast to Arabidopsis thaliana (thale cress) and cyanobacterium Synechocystis that each have only one GGR gene. We also produced rice callus with inactivated OsGGR1 and OsGGR2 that produced T3 but not Toc. Such rice callus could be used as a resource for production of pure T3 for nutraceutical applications.
Comparative genomic and transcriptomic analyses of Family-1 UDP glycosyltransferase in three Brassica species and Arabidopsis indicates stress-responsive regulation
Authors: Rehman Hafiz Mamoon , Nawaz Muhammad Amjad , Shah Zahid Hussain , Ludwig-Müller Jutta , Chung Gyuhwa , Ahmad Muhammad Qadir , Yang Seung Hwan , Lee Soo In
Published: January 2018

In plants, UGTs (UDP-glycosyltransferases) glycosylate various phytohormones and metabolites in response to biotic and abiotic stresses. Little is known about stress-responsive glycosyltransferases in plants. Therefore, it is important to understand the genomic and transcriptomic portfolio of plants with regard to biotic and abiotic stresses. Here, we identified 140, 154, and 251 putative UGTs in Brassica rapa, Brassica oleracea, and Brassica napus, respectively, and clustered them into 14 major phylogenetic groups (A–N). Fourteen major KEGG pathways and 24 biological processes were associated with the UGTs, highlighting them as unique modulators against environmental stimuli. Putative UGTs from B. rapa and B. oleracea showed a negative selection pressure and biased gene fractionation pattern during their evolution. Polyploidization increased the intron proportion and number of UGT-containing introns among Brassica. The putative UGTs were preferentially expressed in developing tissues and at the senescence stage. Differential expression of up- and down-regulated UGTs in response to phytohormone treatments, pathogen responsiveness and abiotic stresses, inferred from microarray and RNA-Seq data in Arabidopsis and Brassica broaden the glycosylation impact at the molecular level. This study identifies unique candidate UGTs for the manipulation of biotic and abiotic stress pathways in Brassica and Arabidopsis.
Computer-aided Discovery of Peptides that Specifically Attack Bacterial Biofilms
Authors: Haney Evan F. , Brito-Sánchez Yoan , Trimble Michael J. , Mansour Sarah C. , Cherkasov Artem , Hancock Robert E. W.
Published: January 2018

Biofilms represent a multicellular growth state of bacteria that are intrinsically resistant to conventional antibiotics. It was recently shown that a synthetic immunomodulatory cationic peptide, 1018 (VRLIVAVRIWRR-NH2), exhibits broad-spectrum antibiofilm activity but the sequence determinants of antibiofilm peptides have not been systematically studied. In the present work, a peptide library consisting of 96 single amino acid substituted variants of 1018 was SPOT-synthesized on cellulose arrays and evaluated against methicillin resistant Staphylococcus aureus (MRSA) biofilms. This dataset was used to establish quantitative structure-activity relationship (QSAR) models relating the antibiofilm activity of these peptides to hundreds of molecular descriptors derived from their sequences. The developed 3D QSAR models then predicted the probability that a peptide would possess antibiofilm activity from a library of 100,000 virtual peptide sequences in silico. A subset of these variants were SPOT-synthesized and their activity assessed, revealing that the QSAR models resulted in ~85% prediction accuracy. Notably, peptide 3002 (ILVRWIRWRIQW-NH2) was identified that exhibited an 8-fold increased antibiofilm potency in vitro compared to 1018 and proved effective in vivo, significantly reducing abscess size in a chronic MRSA mouse infection model. This study demonstrates that QSAR modeling can successfully be used to identify antibiofilm specific peptides with therapeutic potential.
Evaluation of the osteogenesis and osseointegration of titanium alloys coated with graphene: an in vivo study
Authors: Li Kewen , Wang Chunhui , Yan Jinhong , Zhang Qi , Dang Baoping , Wang Zhuo , Yao Yun , Lin Kaifeng , Guo Zhongshang , Bi Long , Han Yisheng
Published: January 2018

The aim of this study was to investigate whether a surface coating with graphene could enhance the surface bioactivation of titanium alloys (Ti6Al4V) to further accelerate in vivo osteogenesis and osseointegration at the implant surface. In this study, a New Zealand white rabbit femoral condyle defect model was established. After 4, 12 and 24 weeks, biomechanical testing, micro-computed tomography (Micro-CT) analyses and histological observations were performed. At the highest push-out forces during the test, microstructure parameters, such as the bone volume/total volume fraction (BV/TV) and mineral apposition rate (MAR), of the new bone were significantly higher in the graphene-coated Ti6Al4V group (G-Ti6Al4V) than in the Ti6Al4V group (P < 0.05). Van Gieson (VG) staining showed that the G-Ti6Al4V group had more new bone formation than the Ti6Al4V group, and the G-Ti6Al4V group showed a closer fit between the bone and implant. In conclusion, graphene might be a novel type of nano-coating material for enhancing the surface biological activity of Ti-based alloy materials and may further promote in vivo osteogenesis and osseointegration.
A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain
Authors: Munro Gordon , Petersen Steffen , Jansen-Olesen Inger , Olesen Jes
Published: January 2018

Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological changes occurring within dural or trigeminal pain circuits. We generated successive generations of a unique inbred rat strain, spontaneous trigeminal allodynia (STA) rats, previously reported to exhibit an episodic migraine-like behavioural phenotype. We show that both male and female STA rats display robust and sustained reductions in periorbital thresholds to cutaneous mechanical stimulation. Otherwise, the general behavior (e.g. locomotor, grooming) of these rats appeared normal. In female STA rats, the mechanical hypersensitivity was confined to the cephalic region, manifested after puberty through adolescence, and was sustained into adulthood recapitulating the clinical manifestation of migraine. We exploited this hitherto unidentified chronic phenotype to show that the migraine-specific drugs sumatriptan (5-HT1B/1D receptor agonist) and olcegepant (CGRP receptor antagonist) could completely reverse cephalic hypersensitivity using a within subject cross-over paradigm. Our findings indicate that STA rats actually possess a phenotype indicative of migraine chronicity which is exquisitely sensitive to migraine therapeutics. This unique strain could prove to be an invaluable resource in preclinical migraine drug discovery.
White matter hyperintensity shape and location feature analysis on brain MRI; proof of principle study in patients with diabetes
Authors: de Bresser Jeroen , Kuijf Hugo J. , Zaanen Karlijn , Viergever Max A. , Hendrikse Jeroen , Biessels Geert Jan ,   Utrecht Vascular Cognitive Impairment Study Group, Algra A. , van den Berg E. , Bouvy W. , Brundel M. , Heringa S. , Kappelle L. J. , Leemans A. , Luijten P. R. , Mali W. P. Th. M. , Rutten G. E. H. M. , Vincken K. L. , Zwanenburg J.
Published: January 2018

Cerebral small vessel disease is a heterogeneous disease in which various underlying etiologies can lead to different types of white matter hyperintensities (WMH). WMH shape features might aid in distinguishing these different types. In this proof of principle study in patients with type 2 diabetes mellitus (T2DM), we present a novel approach to assess WMH using shape features. Our algorithm determines WMH volume and different WMH shape and location features on 3T MRI scans. These features were compared between patients with T2DM (n = 60) and a matched control group (n = 54). Although a more traditional marker (WMH volume) was not significantly different between groups (natural log transformed Beta (95% CI): 0.07 (−0.11↔0.24)), patients with T2DM showed a larger number of non-punctuate WMH (median (10th–90th percentile), patients: 40 lesions per person (16–86); controls: 26 (5–58)) and a different shape (eccentricity) of punctuate deep WMH (Beta (95% CI): 0.40 (0.23↔0.58)) compared to controls. In conclusion, our algorithm identified WMH features that are not part of traditional WMH assessment, but showed to be distinguishing features between patients with T2DM and controls. Future studies could address these features to further unravel the etiology and functional impact of WMH.
Activated Biomass-derived Graphene-based Carbons for Supercapacitors with High Energy and Power Density
Authors: Jung SungHoon , Myung Yusik , Kim Bit Na , Kim In Gyoo , You In-Kyu , Kim TaeYoung
Published: January 2018

Here, we present a facile and low-cost method to produce hierarchically porous graphene-based carbons from a biomass source. Three-dimensional (3D) graphene-based carbons were produced through continuous sequential steps such as the formation and transformation of glucose-based polymers into 3D foam-like structures and their subsequent carbonization to form the corresponding macroporous carbons with thin graphene-based carbon walls of macropores and intersectional carbon skeletons. Physical and chemical activation was then performed on this carbon to create micro- and meso-pores, thereby producing hierarchically porous biomass-derived graphene-based carbons with a high Brunauer-Emmett-Teller specific surface area of 3,657 m2 g−1. Owing to its exceptionally high surface area, interconnected hierarchical pore networks, and a high degree of graphitization, this carbon exhibited a high specific capacitance of 175 F g−1 in ionic liquid electrolyte. A supercapacitor constructed with this carbon yielded a maximum energy density of 74 Wh kg−1 and a maximum power density of 408 kW kg−1, based on the total mass of electrodes, which is comparable to those of the state-of-the-art graphene-based carbons. This approach holds promise for the low-cost and readily scalable production of high performance electrode materials for supercapacitors.
Establishing rapid analysis of Pu isotopes in seawater to study the impact of Fukushima nuclear accident in the Northwest Pacific
Authors: Men Wu , Zheng Jian , Wang Hai , Ni Youyi , Aono Tatsuo , Maxwell Sherrod L. , Tagami Keiko , Uchida Shigeo , Yamada Masatoshi
Published: January 2018

In order to assess the impact of the Fukushima derived Pu isotopes on seawater, a new analytical method to rapidly determine Pu isotopes in seawater by SF-ICP-MS including Fe(OH)2 primary co-precipitation, CaF2/LaF3 secondary co-precipitation and TEVA+UTEVA+DGA extraction chromatographic separation was established. High concentration efficiency (~100%) and high U decontamination factor (~107) were achieved. The plutonium chemical recoveries were 74–88% with the mean of 83 ± 5%. The precisions for both 240Pu/239Pu atom ratios and 239+240Pu activity concentrations were less than 5% when 15 L of seawater samples with the typical 239+240Pu activity of the Northwest Pacific were measured. It just needs 12 hours to determine plutonium using this new method. The limit of detection (LOD) for 239Pu and 240Pu were both 0.08 fg/mL, corresponding to 0.01 mBq/m3 for 239Pu and 0.05 mBq/m3 for 240Pu when a 15 L volume of seawater was measured. This method was applied to determine the seawater samples collected 446–1316 km off the FDNPP accident site in the Northwest Pacific in July of 2013. The obtained 239+240Pu activity concentrations of 1.21–2.19 mBq/m3 and the 240Pu/239Pu atom ratios of 0.198–0.322 suggested that there was no significant Pu contamination from the accident to the Northwest Pacific.
Ergodicity breaking transition in a glassy soft sphere system at small but non-zero temperatures
Authors: Maiti Moumita , Schmiedeberg Michael
Published: January 2018

While the glass transition at non-zero temperature seems to be hard to access for experimental, theoretical, or simulation studies, jamming at zero temperature has been studied in great detail. Motivated by the exploration of the energy landscape that has been successfully used to investigate athermal jamming, we introduce a new method that includes the possibility of the thermally excited crossing of energy barriers. We then determine whether the ground state configurations of a soft sphere system are accessible or not and as a consequence whether the system is ergodic or effectively non-ergodic. Interestingly, we find an transition where the system becomes effectively non-ergodic if the density is increased. The transition density in the limit of small but non-zero temperatures is independent of temperature and below the transition density of athermal jamming. This confirms recent computer simulation studies where athermal jamming occurs deep inside the glass phase. In addition, we show that the ergodicity breaking transition is in the universality class of directed percolation. Therefore, our approach not only makes the transition from an ergodic to an effectively non-ergodic systems easily accessible and helps to reveal its universality class but also shows that it is fundamentally different from athermal jamming.
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Authors: Pagerols Mireia , Richarte Vanesa , Sánchez-Mora Cristina , Rovira Paula , Soler Artigas María , Garcia-Martínez Iris , Calvo-Sánchez Eva , Corrales Montse , da Silva Bruna Santos , Mota Nina Roth , Victor Marcelo Moraes , Rohde Luis Augusto , Grevet Eugenio Horacio , Bau Claiton Henrique Dotto , Cormand Bru , Casas Miguel , Ramos-Quiroga Josep Antoni , Ribasés Marta
Published: January 2018

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies.
Eye region surface temperature reflects both energy reserves and circulating glucocorticoids in a wild bird
Authors: Jerem Paul , Jenni-Eiermann Susanne , Herborn Katherine , McKeegan Dorothy , McCafferty Dominic J. , Nager Ruedi G.
Published: January 2018

Body temperature of endotherms shows substantial within- and between-individual variation, but the sources of this variation are not fully understood in wild animals. Variation in body temperature can indicate how individuals cope with their environment via metabolic or stress-induced effects, both of which may relate to depletion of energy reserves. Body condition can reflect heat production through changes to metabolic rate made to protect energy reserves. Additionally, changes in metabolic processes may be mediated by stress-related glucocorticoid secretion, which is associated with altered blood-flow patterns that affect regional body temperatures. Accordingly, both body condition and glucocorticoid secretion should relate to body temperature. We used thermal imaging, a novel non-invasive method of temperature measurement, to investigate relationships between body condition, glucocorticoid secretion and body surface temperature in wild blue tits (Cyanistes caeruleus). Individuals with lower body condition had lower eye-region surface temperature in both non-breeding and breeding seasons. Eye-region surface temperature was also negatively correlated with baseline circulating glucocorticoid levels in non-breeding birds. Our results demonstrate that body surface temperature can integrate multiple aspects of physiological state. Consequently, remotely-measured body surface temperature could be used to assess such aspects of physiological state non-invasively in free-living animals at multiple life history stages.