bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Dependence of the Liquidus and Solidus Temperatures in the Fe‐P Binary System Determined by In Situ Ultrasonics: Implications to the Solidification of Fe‐P Liquids in Planetary Cores
Authors: Chantel Julien , Jing Zhicheng , Xu Man , Yu Tony , Wang Yanbin
Published: April 2018

We have developed a new technique for determining the liquidus and eutectic (or solidus) temperatures of Fe‐light element alloys at high pressures in a multianvil apparatus, by studying ultrasonic wave propagation through the sample. While the onset of melting is manifested by the loss of both compressional (P‐) and shear (S‐) wave signals due to the scattering of sound waves by partial melts, the completion of melting is confirmed by the reappearance of the P wave signal when the scattering due to residual crystals disappears. By applying this technique to the Fe‐P binary system with three different phosphorus contents, we were able to constrain the Fe‐rich portion of the phase diagram up to 7 GPa and 1,733 K. Our results show that for phosphorus‐poor compositions, ranging from Fe‐5wt%P to the eutectic composition, the liquidus temperature exhibits a weak negative pressure dependence (dT/dP = −10.4 K GPa−1 for Fe‐5wt%P). While for the phosphorus‐richer compositions, including Fe‐10wt%P and Fe3P, the liquidus temperature increases significantly with pressure (dT/dP = 71.3 and 62.5 K GPa−1, respectively). This indicates a shift of the eutectic composition to lower phosphorus contents with increasing pressure. Consequently, molten metallic cores of planetary bodies with phosphorus contents ranging from Fe‐5wt%P to the eutectic composition would start crystallization from the top of the core and proceed downward. Whereas cores with phosphorus‐richer compositions (Fe‐10wt%P to Fe3P) would undergo a bottom‐up crystallization, resulting in a growing solid inner core.
How Fast Is the Nile Delta Sinking?
Authors: Underwood Emily
Published: April 2018

New study calculates the delta’s subsidence on the basis of satellite data.
Real-life achievement of lipid-lowering treatment targets in the DIAbetes and LifEstyle Cohort Twente: systemic assessment of pharmacological and nutritional factors
Authors: Gant Christina M. , Binnenmars S. Heleen , Harmelink Manon , Soedamah-Muthu Sabita S. , Bakker Stephan J. L. , Navis Gerjan , Laverman Gozewijn D.
Published: April 2018

Background/Objectives

Lowering low-density lipoprotein cholesterol (LDLc) in type 2 diabetes mellitus is of paramount importance in preventing cardiovascular disease. However, treatment targets for LDLc are often not reached. We studied the prevalence of LDLc target achievement in a real-life population of type 2 diabetes mellitus patients in secondary care, and investigated whether in those not on target, there is room for intensifying pharmacological and lifestyle management according to current treatment guidelines.

Subjects/Methods

We performed a cross-sectional analysis in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1; n = 450, age 63 ± 9 years, 58% men, diabetes duration 11 (7–18) years). At baseline, we determined plasma LDLc concentration, pharmacological treatment (i.e., statin use), and lifestyle (physical activity and dietary intake). Patients were divided according to LDLc < 1.8, LDLc 1.8–2.5, and LDLc > 2.5 mmol/l. Dietary intake was collected from a validated Food Frequency Questionnaire (177 items) and we determined guideline adherence for different food groups. Physical activity was assessed with the Short Questionnaire to ASsess Health enhancing behavior.

Results

LDLc data were available in 428 type 2 diabetes mellitus patients. LDLc ≤ 2.5 mmol/l was achieved in 317 patients (76%). In total, 76% of patients used statins, in those with LDLc > 2.5 mmol/l, this was 44%. Adherence to lifestyle guidelines was not different between the LDLc groups and was as follows: body mass index 6%, physical activity 59%, vegetables 7%, fruit 28%, legumes 59%, nuts 14%, dairy 19%, fish 36%, tea 8%, fats 66%, red meat 12%, processed meat 2%, alcohol 71%, sweetened beverages 34%, and sodium 12%.

Conclusions

In type 2 diabetes mellitus patients in secondary health care, the target LDLc is achieved by three quarters of patients. Increasing statin treatment could be a first step to improve LDLc. In addition, there are ample opportunities for lifestyle management through increasing adherence to lifestyle guidelines.
Dietary patterns and type 2 diabetes among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study
Authors: Galbete Cecilia , Nicolaou Mary , Meeks Karlijn , Klipstein-Grobusch Kerstin , de-Graft Aikins Ama , Addo Juliet , Amoah Stephen K. , Smeeth Liam , Owusu-Dabo Ellis , Spranger Joachim , Agyemang Charles , Mockenhaupt Frank P. , Beune Erik , Stronks Karien , Schulze Matthias B. , Danquah Ina
Published: April 2018

Background/objectives

We aimed to study the associations of dietary patterns (DPs) with type 2 diabetes (T2D) among Ghanaian adults.

Subjects/methods

In the multi-centre, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study (n = 4543), three overall DPs (“mixed”, “rice, pasta, meat and fish,” and “roots, tubers and plantain”) and two site-specific DPs per study site (rural Ghana, urban Ghana and Europe) were identified by principal component analysis. The DPs–T2D associations were calculated by logistic regression models.

Results

Higher adherence to the “rice, pasta, meat and fish” DP (characterized by legumes, rice/pasta, meat, fish, cakes/sweets, condiments) was associated with decreased odds of T2D, adjusted for socio-demographic factors, total energy intake and adiposity measures (odds ratio (OR)per 1 SD = 0.80; 95% confidence interval (CI) = 0.70–0.92). Similar DPs and T2D associations were discernible in urban Ghana and Europe. In the total study population, neither the “mixed” DP (whole grain cereals, sweet spreads, dairy products, potatoes, vegetables, poultry, coffee/tea, sodas/juices, olive oil) nor the “roots, tubers and plantain” DP (refined cereals, fruits, nuts/seeds, roots/tubers/plantain, fermented maize products, legumes, palm oil, condiments) was associated with T2D. Yet, after the exclusion of individuals with self-reported T2D, the “roots, tubers and plantain” DP was inversely associated with T2D (ORper 1 SD = 0.88; 95% CI = 0.69–1.12).

Conclusion

In this Ghanaian population, DPs characterized by the intake of legumes, fish, meat and confectionery were inversely associated with T2D. The effect of a traditional-oriented diet (typical staples, vegetables and legumes) remains unclear.
Human adipose tissue protein analyses using capillary western blot technology
Authors: Lu Jin , Allred Carolyn C. , Jensen Michael D.
Published: April 2018

A capillary western blot (Wes®) technology has recently been validated for analyses of cell culture lysate proteins, but whether it is reliable for human tissue proteins is unknown. We compared traditional western blotting to the Wes® capillary western method to quantitate the relative amount of human adipose tissue CD36, the ratio of phosphorylated Erk1/2 (pErk1/2) to total Erk1/2 during insulin clamp or after niacin treatment and the fold increase in pAktS473 (Akt phosphorylation on Ser473) in response to feeding. The results from these two methods were highly correlated (r = 0.932 for CD36, r = 0.905 for pErk1/2:Erk1/2, r = 0.923 for the change in pAkt/Akt, P < 0.001). On Wes® we observed the distinct peaks around the expected molecular weights for these proteins with decreasing peak areas with serial dilutions of loading protein amount. Wes® and traditional western blot both had linear dynamic ranges for CD36, Erk1/2 and Akt. Due to differences in signal responsiveness for pAkt/Akt, we employed a calibrator sample and log transformation of data to allow proper comparisons. The Wes® approach required less sample than the traditional western blot and less technician/assay time, while achieving high sensitivity and good reproducibility. Capillary western technology (Wes®) provides a satisfactory alternative for analyses of human adipose tissue proteins.
Cascading effects on bacterial communities: cattle grazing causes a shift in the microbiome of a herbivorous caterpillar
Authors: Berman Tali S , Laviad-Shitrit Sivan , Lalzar Maya , Halpern Malka , Inbar Moshe
Published: April 2018

Large mammalian herbivores greatly influence the functioning of grassland ecosystems. Through plant consumption, excreta, and trampling, they modify biodiversity, nutrient cycling, and soil properties. Grazing mammals can also alter soil and rhizosphere bacterial communities, but their effect on the microbiome of other animals in the habitat (i.e., insects) is unknown. Using an experimental field approach and Illumina MiSeq 16S rRNA gene sequencing, we analyzed the influence of cattle grazing on the microbial community of spring webworm caterpillars, Ocnogyna loewii. Our experimental setup included replicated grazed and non-grazed paddocks from which caterpillars were collected twice (first-second and fourth-fifth instar). The caterpillars’ microbiome is composed mostly of Proteobacteria and Firmicutes, and contains a potential symbiont from the genus Carnobacterium (55% of reads). We found that grazing significantly altered the microbiome composition of late instar caterpillars, probably through changes in diet (plant) composition and availability. Furthermore, the microbiome composition of early instar caterpillars significantly differed from late instar caterpillars in 221 OTUs (58 genera). Pseudomonas and Acinetobacter were dominant in early instars, while Carnobacterium and Acinetobacter were dominant in late instars. This study provides new ecological perspectives on the cascading effects mammalian herbivores may have on the microbiome of other animals in their shared habitat.
Daratumumab, lenalidomide, and dexamethasone in East Asian patients with relapsed or refractory multiple myeloma: subgroup analyses of the phase 3 POLLUX study
Authors: Suzuki Kenshi , Dimopoulos Meletios A. , Takezako Naoki , Okamoto Shinichiro , Shinagawa Atsushi , Matsumoto Morio , Kosugi Hiroshi , Yoon Sung-Soo , Huang Shang-Yi , Qin Xiang , Qi Ming , Iida Shinsuke
Published: April 2018

In the phase 3 POLLUX study, daratumumab plus lenalidomide and dexamethasone (DRd) significantly reduced the risk of progression/death and induced deeper responses vs. lenalidomide and dexamethasone alone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM). We report a subgroup analysis of East Asian (Japanese, Korean, and Taiwanese) patients from POLLUX based on a longer follow-up of 24.7 months. Median progression-free survival was not reached (NR) for DRd vs. 13.8 months for Rd (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.23–0.76), and overall response rates were higher for DRd vs. Rd (90.2 vs. 72.1%). DRd extended the median duration of response vs. Rd (NR vs. 20.2 months), and minimal residual disease–negative rates at the 10–5 sensitivity threshold were 21.2 vs. 9.1% for DRd vs. Rd. No new safety signals were observed. Similar efficacy and safety were observed in the smaller subgroup of Japanese patients treated with DRd vs. Rd. These results demonstrate favorable efficacy and safety of DRd vs. Rd in East Asian patients and also in the Japanese-only patient subgroup that are consistent with findings in the overall patient population of POLLUX.
IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE
Authors: Wang Shu , Wang Jingya , Kumar Varsha , Karnell Jodi L. , Naiman Brian , Gross Phillip S. , Rahman Saifur , Zerrouki Kamelia , Hanna Richard , Morehouse Christopher , Holoweckyj Nicholas , Liu Hao ,   Autoimmunity Molecular Medicine Team, Casey Kerry , Smith Michael , Parker Melissa , White Natalie , Riggs Jeffrey , Ward Beth , Bhat Geetha , Rajan Bhargavi , Grady Rebecca , Groves Chris , Manna Zerai , Goldbach-Mansky Raphaela , Hasni Sarfaraz , Siegel Richard , Sanjuan Miguel , Streicher Katie , Cancro Michael P. , Kolbeck Roland , Ettinger Rachel
Published: April 2018

Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chiT-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11chiT-bet+ B cells in human SLE.
Non-canonical activation of DAPK2 by AMPK constitutes a new pathway linking metabolic stress to autophagy
Authors: Shiloh Ruth , Gilad Yuval , Ber Yaara , Eisenstein Miriam , Aweida Dina , Bialik Shani , Cohen Shenhav , Kimchi Adi
Published: April 2018

Autophagy is an intracellular degradation process essential for adaptation to metabolic stress. DAPK2 is a calmodulin-regulated protein kinase, which has been implicated in autophagy regulation, though the mechanism is unclear. Here, we show that the central metabolic sensor, AMPK, phosphorylates DAPK2 at a critical site in the protein structure, between the catalytic and the calmodulin-binding domains. This phosphorylation activates DAPK2 by functionally mimicking calmodulin binding and mitigating an inhibitory autophosphorylation, providing a novel, alternative mechanism for DAPK2 activation during metabolic stress. In addition, we show that DAPK2 phosphorylates the core autophagic machinery protein, Beclin-1, leading to dissociation of its inhibitor, Bcl-XL. Importantly, phosphorylation of DAPK2 by AMPK enhances DAPK2’s ability to phosphorylate Beclin-1, and depletion of DAPK2 reduces autophagy in response to AMPK activation. Our study reveals a unique calmodulin-independent mechanism for DAPK2 activation, critical to its function as a novel downstream effector of AMPK in autophagy.
Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models
Authors: St Clair Joshua R. , Ramirez David , Passman Samantha , Benninger Richard K. P.
Published: April 2018

In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
Impact of alkali on the passivation of silicate glass
Authors: Collin Marie , Fournier Maxime , Charpentier Thibault , Moskura Mélanie , Gin Stéphane
Published: April 2018

Amorphous silica-rich surface layers, also called gels, can passivate silicate glass and minerals depending on environmental conditions. However, several uncertainties remain on the mechanisms controlling the formation of these layers. In this paper, the influence of exogenous ions supplied by solutions is studied, both on the formation and on the properties of the gel formed on international simple glass (ISG). ISG was altered at 90 °C, pH90 °C 7, in silica-saturated solutions containing various alkaline cations separately (Li+, Na+, K+, and Cs+). The alteration kinetics observed with Li and Na in the solution is similar to that observed with no ions, while K and Cs in the solution tend to decrease glass alteration. Furthermore, for K or Cs ions, the kinetics decreases as the ionic strength of the solution increases. The passivation layer formed in these solutions shows a selectivity toward cations following the series K > Cs > Na >> Li. These alkalis replace Ca from pristine glass in the altered structures, leading to differences in [AlO4]− units charge compensation. Importantly, exchange between Ca and alkali also affects the total quantity of water inside each gel and this effect is well correlated with the observed drop in glass alteration.
Publisher Correction: A new antagonist for CCR4 attenuates allergic lung inflammation in a mouse model of asthma
Authors: Zhang Yang , Wu Yinfang , Qi Hui , Xiao Junhai , Gong Hongwei , Zhang Yan , Xu Enquan , Li Song , Ma Dalong , Wang Ying , Li Wen , Shen Huahao
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Direct observation of multiple conformational states in Cytochrome P450 oxidoreductase and their modulation by membrane environment and ionic strength
Authors: Bavishi Krutika , Li Darui , Eiersholt Stine , Hooley Emma N. , Petersen Troels C. , Møller Birger Lindberg , Hatzakis Nikos S. , Laursen Tomas
Published: April 2018

Cytochrome P450 oxidoreductase (POR) is the primary electron donor in eukaryotic cytochrome P450 (CYP) containing systems. A wealth of ensemble biophysical studies of Cytochrome P450 oxidoreductase (POR) has reported a binary model of the conformational equilibrium directing its catalytic efficiency and biomolecular recognition. In this study, full length POR from the crop plant Sorghum bicolor was site-specifically labeled with Cy3 (donor) and Cy5 (acceptor) fluorophores and reconstituted in nanodiscs. Our single molecule fluorescence resonance energy transfer (smFRET) burst analyses of POR allowed the direct observation and quantification of at least three dominant conformational sub-populations, their distribution and occupancies. Moreover, the state occupancies were remodeled significantly by ionic strength and the nature of reconstitution environment, i.e. phospholipid bilayers (nanodiscs) composed of different lipid head group charges vs. detergent micelles. The existence of conformational heterogeneity in POR may mediate selective activation of multiple downstream electron acceptors and association in complexes in the ER membrane.
Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients
Authors: Douillard Aymeric , Picot Marie-Christine , Delcourt Cécile , Defoort-Dhellemmes Sabine , Marzouka Nour Al-Dain , Lacroux Annie , Zanlonghi Xavier , Drumare Isabelle , Jozefowicz Elsa , Bocquet Béatrice , Baudoin Corinne , Perez-Roustit Sarah , Arsène Sophie , Gissot Valérie , Devin François , Arndt Carl , Wolff Benjamin , Mauget-Faÿsse Martine , Quaranta Maddalena , Mura Thibault , Deplanque Dominique , Oubraham Hassiba , Cohen Salomon Yves , Gastaud Pierre , Zambrowski Olivia , Creuzot-Garcher Catherine , Saïd Saddek Mohand , Sahel José-Alain , Souied Eric , Milazzo Solange , Garavito Rocio Blanco , Kalatzis Vasiliki , Puech Bernard , Hamel Christian , Audo Isabelle , Meunier Isabelle
Published: April 2018

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d’Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.
Optically Tunable Gratings Based on Coherent Population Oscillation
Authors: Zhang Xiao-Jun , Wang Hai-Hua , Wang Lei , Wu Jin-Hui
Published: April 2018

We theoretically study the optically tunable gratings based on a L-type atomic medium using coherent population oscillations from the angle of reflection and transmission of the probe field. Adopting a standing-wave driving field, the refractive index of the medium as well as the absorption are periodically modified. Consequently, the Bragg scattering causes the effective reflection. We show that different intensities of the control field lead to three types of reflection profile which actually correspond to different absorption/amplification features of the medium. We present a detailed analyses about the influence of amplification on the reflection profile as well. The coherent population oscillation is robust to the dephasing effect, and such induced gratings could have promising applications in nonlinear optics and all-optical information processing.
Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue
Authors: Abu Hamdeh Sami , Shevchenko Ganna , Mi Jia , Musunuri Sravani , Bergquist Jonas , Marklund Niklas
Published: April 2018

The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.
Inferring a nonlinear biochemical network model from a heterogeneous single-cell time course data
Authors: Shindo Yuki , Kondo Yohei , Sako Yasushi
Published: April 2018

Mathematical modeling and analysis of biochemical reaction networks are key routines in computational systems biology and biophysics; however, it remains difficult to choose the most valid model. Here, we propose a computational framework for data-driven and systematic inference of a nonlinear biochemical network model. The framework is based on the expectation-maximization algorithm combined with particle smoother and sparse regularization techniques. In this method, a “redundant” model consisting of an excessive number of nodes and regulatory paths is iteratively updated by eliminating unnecessary paths, resulting in an inference of the most likely model. Using artificial single-cell time-course data showing heterogeneous oscillatory behaviors, we demonstrated that this algorithm successfully inferred the true network without any prior knowledge of network topology or parameter values. Furthermore, we showed that both the regulatory paths among nodes and the optimal number of nodes in the network could be systematically determined. The method presented in this study provides a general framework for inferring a nonlinear biochemical network model from heterogeneous single-cell time-course data.
Aldosterone Impairs Mitochondrial Function in Human Cardiac Fibroblasts via A-Kinase Anchor Protein 12
Authors: Ibarrola Jaime , Sadaba Rafael , Martinez-Martinez Ernesto , Garcia-Peña Amaia , Arrieta Vanessa , Alvarez Virginia , Fernández-Celis Amaya , Gainza Alicia , Cachofeiro Victoria , Santamaria Enrique , Fernandez-Irigoyen Joaquin , Jaisser Frederic , Lopez-Andres Natalia
Published: April 2018

Aldosterone (Aldo) contributes to mitochondrial dysfunction and cardiac oxidative stress. Using a proteomic approach, A-kinase anchor protein (AKAP)-12 has been identified as a down-regulated protein by Aldo in human cardiac fibroblasts. We aim to characterize whether AKAP-12 down-regulation could be a deleterious mechanism which induces mitochondrial dysfunction and oxidative stress in cardiac cells. Aldo down-regulated AKAP-12 via its mineralocorticoid receptor, increased oxidative stress and induced mitochondrial dysfunction characterized by decreased mitochondrial-DNA and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions in human cardiac fibroblasts. CRISPR/Cas9-mediated knock-down of AKAP-12 produced similar deleterious effects in human cardiac fibroblasts. CRISPR/Cas9-mediated activation of AKAP-12 blunted Aldo effects on mitochondrial dysfunction and oxidative stress in human cardiac fibroblasts. In Aldo-salt-treated rats, cardiac AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased and paralleled increased oxidative stress. In myocardial biopsies from patients with aortic stenosis (AS, n = 26), AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased as compared to Controls (n = 13). Circulating Aldo levels inversely correlated with cardiac AKAP-12. PGC-1α positively associated with AKAP-12 and with mitochondrial-DNA. Aldo decreased AKAP-12 expression, impairing mitochondrial biogenesis and increasing cardiac oxidative stress. AKAP-12 down-regulation triggered by Aldo may represent an important event in the development of mitochondrial dysfunction and cardiac oxidative stress.
Up-regulation of microRNA-203 in influenza A virus infection inhibits viral replication by targeting DR1
Authors: Zhang Sen , Li Jing , Li Junfeng , Yang Yinhui , Kang Xiaoping , Li Yuchang , Wu Xiaoyan , Zhu Qingyu , Zhou Yusen , Hu Yi
Published: April 2018

MicroRNAs (miRNAs) are small noncoding RNA molecules that play important roles in various biological processes. Much evidence shows that miRNAs are closely associated with numerous virus infections; however, involvement of cellular miRNAs in influenza A virus (IAV) infection is unclear. Here, we found that expression of miR-203 was up-regulated markedly via two different mechanisms during IAV infection. First, we examined the effects of type I interferon induced by IAV on direct activation of miR-203 expression. Next, we showed that DNA demethylation within the miR-203 promoter region in A549 cells induced its up-regulation, and that expression of DNA methyltransferase 1 was down-regulated following H5N1 virus infection. Ectopic expression of miR-203 in turn inhibited H5N1 virus replication by targeting down-regulator of transcription 1 (DR1), which was identified as a novel target of miR-203. Silencing DR1 in miR-203 knockout cells using a specific siRNA inhibited replication of the H5N1 virus, an effect similar to that of miR-203. In summary, the data show that host cell expression of miR-203 is up-regulated upon IAV infection, which increases antiviral responses by suppressing a novel target gene, DR1. Thus, we have identified a novel mechanism underlying the relationship between miR-203 and IAV infection.
Growth differentiation factor 15 ameliorates nonalcoholic steatohepatitis and related metabolic disorders in mice
Authors: Kim Kook Hwan , Kim Seong Hun , Han Dai Hoon , Jo Young Suk , Lee Yong-ho , Lee Myung-Shik
Published: April 2018

Growth differentiation factor 15 (GDF15) is an endocrine hormone belonging to the TGFβ superfamily member. GDF15 administration or GDF15 overexpression has been reported to have anti-obesity and anti-diabetic effects. Although non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is frequently associated with obesity and insulin resistance, the functional role of endogenous GDF15 and therapeutic effect of GDF15 overexpression in NASH and related metabolic deterioration have not been evaluated. Here, we found that GDF15 expression was increased in the livers of NASH animal models and human subjects with NASH. Elevated expression of GDF15 was due to diet-induced hepatic endoplasmic reticulum (ER) stress. Gdf15-knockout mice exhibited aggravated NASH phenotypes such as increased steatosis, hepatic inflammation, fibrosis, liver injury, and metabolic deterioration. Furthermore, GDF15 directly suppressed expression of fibrosis-related genes and osteopontin (OPN), contributing factors for NASH-related fibrosis, in hepatic stellate cells in vitro and in the liver of mice in vivo. Finally, we found that GDF15-transgenic mice showed attenuation of NASH phenotypes and metabolic deterioration. Therefore, our results suggest that induction of endogenous GDF15 is a compensatory mechanism to protect against the progression of NASH and that GDF15 could be an attractive therapeutic candidate for treatment of NASH and NASH-related metabolic deterioration.
Variations of Prevalence and Incidence of Atrial Fibrillation and Oral Anticoagulation Rate According to Different Analysis Approaches
Authors: Yang Pil-Sung , Ryu Soorack , Kim Daehoon , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Hwang Jinseub , Joung Boyoung , Lip Gregory Y. H.
Published: April 2018

The reported incidence and prevalence of atrial fibrillation (AF) has been inconsistent across published studies. Using the National Health Insurance Service database of Korea, the prevalence and incidence of AF, and oral anticoagulation (OAC) use of AF patients were explored according to three different approaches; ‘formal approach’, considering individual AF diagnosis and mortality; ‘limited diagnosis approach’, using upper 5 main diagnosis; and ‘medical use approach’, using the number of medical use AF population by year without considering individual AF history and mortality. The AF prevalence progressively increased by 2.46-fold from 0.50% in 2004 to 1.54% in 2015 when using a ‘formal approach’ (p for trend <0.001). The overall prevalence was 1.09% and 0.97% when using a ‘formal approach’ and ‘limited diagnosis approaches’, respectively. Overall prevalence decreased to 0.52% with a ‘medical use approach’. The trend of annual AF incidence was stable when using a ‘formal approach’, but increased by 15% when using a ‘medical use approach’. OAC rate in 2015 was 2.1 times higher when using a ‘medical use approach’ compared to using a ‘formal approach’ (40.3% vs. 19.1%, p < 0.001). Given the wide variability in prevalence and incidence figures with different analysis approaches, careful attention to the analysis methodology is needed.
Effect of the sodium–glucose cotransporter 2 inhibitor luseogliflozin on pancreatic beta cell mass in db/db mice of different ages
Authors: Takahashi Kiyohiko , Nakamura Akinobu , Miyoshi Hideaki , Nomoto Hiroshi , Kitao Naoyuki , Omori Kazuno , Yamamoto Kohei , Cho Kyu Yong , Terauchi Yasuo , Atsumi Tatsuya
Published: April 2018

To examine the effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on pancreatic beta cell mass in db/db mice of different ages. db/db mice aged 6, 10, 14 and 24 weeks old were fed either standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group). After 4 weeks, immunohistochemistry and gene expression tests were conducted. In 6-week-old db/db mice, immunohistochemistry revealed a significant increase in beta cell mass in the luseo group compared with the control group after 4 weeks of treatment. Gene expression profiling of isolated islets showed upregulation Mafa, Pdx1, Ki67 and Ccnd2 in the luseo group. Beta cell mass decreased with age in db/db mice in the control group. Beta cell mass in the luseo group significantly increased compared with the control group regardless of age, although beta cell mass in the 28-week-old luseo group (4 weeks of treatment in 24-week-old db/db mice) was significantly lower than in the 10-week-old luseo group (4 weeks of treatment in 6-week-old db/db mice). Luseogliflozin preserved beta cell mass in db/db mice. The protective effect was more evident in the earlier phase of diabetes.
Neural and behavioural correlates of repeated social defeat
Authors: Butler Julie M. , Whitlow Sarah M. , Roberts David A. , Maruska Karen P.
Published: April 2018

Dominance hierarchies are common across the animal kingdom and have important consequences for reproduction and survival. Animals of lower social status cope with repeated social defeat using proactive and reactive behaviours. However, there remains a paucity of information on how an individual’s coping behaviours changes over time or what neural mechanisms are involved. We used a resident-intruder paradigm in the African cichlid fish Astatotilapia burtoni to investigate the neural correlates of these two opposing behaviour groups. Fish initially used both proactive and reactive behaviours, but had a dramatic increase in use of proactive behaviours during the third interaction, and this was followed by cessation of proactive behaviours and exclusive use of reactive coping. By quantifying neural activation in socially-relevant brain regions, we identify a subset of brain nuclei, including those homologous to the mammalian amygdala, showing higher activation in fish displaying proactive but not reactive behaviours. Fish displaying reactive behaviours had greater neural activation in the superior raphe, suggesting a possible conserved function during social defeat across vertebrates. These data provide the first evidence on the involvement of specific brain regions underlying proactive and reactive coping in fishes, indicating that these nuclei have conserved functions during social defeat across taxa.
Publisher Correction: Cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases
Authors: Kahl Anja , Blanco Ismary , Jackman Katherine , Baskar Juhi , Mohan Harihar Milaganur , Rodney-Sandy Reunet , Zhang Sheng , Iadecola Costantino , Hochrainer Karin
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Progression of Post-Traumatic Osteoarthritis in rat meniscectomy models: Comprehensive monitoring using MRI
Authors: Ali Tonima S. , Prasadam Indira , Xiao Yin , Momot Konstantin I.
Published: April 2018

Knee injury often triggers post-traumatic osteoarthritis (PTOA) that affects articular cartilage (AC), subchondral bone, meniscus and the synovial membrane. The available treatments for PTOA are largely ineffective due to late diagnosis past the “treatment window”. This study aimed to develop a detailed understanding of the time line of the progression of PTOA in murine models through longitudinal observation of the femorotibial joint from the onset of the disease to the advanced stage. Quantitative magnetic resonance microimaging (µMRI) and histology were used to evaluate PTOA-associated changes in the knee joints of rats subjected to knee meniscectomy. Systematic longitudinal changes in the articular cartilage thickness, cartilage T2 and the T2 of epiphysis within medial condyles of the tibia were all found to be associated with the development of PTOA in the animals. The following pathogenesis cascade was found to precede advanced PTOA: meniscal injury → AC swelling → subchondral bone remodelling → proteoglycan depletion → free water influx → cartilage erosion. Importantly, the imaging protocol used was entirely MRI-based. This protocol is potentially suitable for whole-knee longitudinal, non-invasive assessment of the development of OA. The results of this work will inform the improvement of the imaging methods for early diagnosis of PTOA.
Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities
Authors: Seferovic Maxim , Sánchez-San Martín Claudia , Tardif Suzette D. , Rutherford Julienne , Castro Eumenia C. C. , Li Tony , Hodara Vida L. , Parodi Laura M. , Giavedoni Luis , Layne-Colon Donna , Tamhankar Manasi , Yagi Shigeo , Martyn Calla , Reyes Kevin , Suter Melissa A. , Aagaard Kjersti M. , Chiu Charles Y. , Patterson Jean L.
Published: April 2018

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16–18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.
Robustness of cortical and subcortical processing in the presence of natural masking sounds
Authors: Beetz M. Jerome , García-Rosales Francisco , Kössl Manfred , Hechavarría Julio C.
Published: April 2018

Processing of ethologically relevant stimuli could be interfered by non-relevant stimuli. Animals have behavioral adaptations to reduce signal interference. It is largely unexplored whether the behavioral adaptations facilitate neuronal processing of relevant stimuli. Here, we characterize behavioral adaptations in the presence of biotic noise in the echolocating bat Carollia perspicillata and we show that the behavioral adaptations could facilitate neuronal processing of biosonar information. According to the echolocation behavior, bats need to extract their own signals in the presence of vocalizations from conspecifics. With playback experiments, we demonstrate that C. perspicillata increases the sensory acquisition rate by emitting groups of echolocation calls when flying in noisy environments. Our neurophysiological results from the auditory midbrain and cortex show that the high sensory acquisition rate does not vastly increase neuronal suppression and that the response to an echolocation sequence is partially preserved in the presence of biosonar signals from conspecifics.
Paraneoplastic limbic encephalitis associated with lung cancer
Authors: Shen Kaini , Xu Yan , Guan Hongzhi , Zhong Wei , Chen Minjiang , Zhao Jing , Li Longyun , Wang Mengzhao
Published: April 2018

Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in lung cancer patients. We retrospectively investigated the clinical characteristics, treatment responses, and prognoses in 16 PLE patients who were subsequently diagnosed with lung cancer. Fifteen patients initially presented with disturbance of consciousness, 13 with disorientation, and 12 with seizures. Thirteen patients had autoantibodies, including eight with gamma aminobutyric acid B receptor (GABABR) antibodies and eight with Hu antibodies. PET-CT revealed lung neoplasms in 13 patients, nine of whom exhibited abnormal metabolic activity in the temporal lobe and hippocampus. Fifteen cases were confirmed as limited-stage small cell lung cancer and one as stage IV large cell neuroendocrine carcinoma. Eleven patients received immunomodulatory therapy, and four showed neurological improvement, who all had antibodies against GABABR. Fifteen patients received chemotherapy, of which 14 maintained or improved their PLE status. The overall cancer response rate was 75%, and two-year overall survival was 74.7%. Our results suggest patients with GABAB encephalitis might respond better to immunotherapy than the classical PLE patients with anti-Hu antibodies. Anti-cancer treatment could further improve neurological symptoms. Lung cancer patients with PLE, especially those in limited stage, might have better outcome due to earlier diagnosis and prompt anti-cancer treatment.
Strong contributions of local background climate to the cooling effect of urban green vegetation
Authors: Yu Zhaowu , Xu Shaobin , Zhang Yuhan , Jørgensen Gertrud , Vejre Henrik
Published: April 2018

Utilization of urban green vegetation (UGV) has been recognized as a promising option to mitigate urban heat island (UHI) effect. While we still lack understanding of the contributions of local background climate to the cooling effect of UGV. Here we proposed and employed a cooling effect framework and selected eight typical cities located in Temperate Monsoon Climate (TMC) and Mediterranean Climate (MC) demonstrate that local climate condition largely affects the cooling effect of UGV. Specifically, we found increasing (artificial) rainfall and irrigation contribute to improving the cooling intensity of grassland in both climates, particularly in the hot-dry environment. The cities with high relative humidity would restrict the cooling effect of UGV. Increasing wind speed would significantly enhance the tree-covered while weakening the grass-covered UGVs’ cooling effect in MC cities. We also identified that, in order to achieve the most effective cooling with the smallest sized tree-covered UGV, the area of trees in both climate zones’ cities should generally be planned around 0.5 ha. The method and results enhance understanding of the cooling effect of UGVs on larger (climate) scales and provide important insights for UGV planning and management.
Strain relaxation via formation of cracks in compositionally modulated two-dimensional semiconductor alloys
Authors: Taghinejad Hossein , Eftekhar Ali A. , Campbell Philip M. , Beatty Brian , Taghinejad Mohammad , Zhou Yao , Perini Christopher J. , Moradinejad Hesam , Henderson Walter E. , Woods Eric V. , Zhang Xiang , Ajayan Pulickel , Reed Evan J. , Vogel Eric M. , Adibi Ali
Published: April 2018

Composition modulation of two-dimensional transition-metal dichalcogenides (TMDs) has introduced an enticing prospect for the synthesis of Van der Waals alloys and lateral heterostructures with tunable optoelectronic properties. Phenomenologically, the optoelectronic properties of alloys are entangled to a strain that is intrinsic to synthesis processes. Here, we report an unprecedented biaxial strain that stems from the composition modulation of monolayer TMD alloys (e.g., MoS2xSe2(1 - x)) and inflicts fracture on the crystals. We find that the starting crystal (MoSe2) fails to adjust its lattice constant as the atoms of the host crystal (selenium) are replaced by foreign atoms (sulfur) during the alloying process. Thus, the resulting alloy forms a stretched lattice and experiences a large biaxial tensile strain. Our experiments show that the biaxial strain relaxes via formation of cracks in interior crystal domains or through less constraint bounds at the edge of the monolayer alloys. Griffith’s criterion suggests that defects combined with a sulfur-rich environment have the potential to significantly reduce the critical strain at which cracking occurs. Our calculations demonstrate a substantial reduction in fracture-inducing critical strain from 11% (in standard TMD crystals) to a range below 4% in as-synthesized alloys.
Molecularly Imprinted Polymers-based Separation and Sensing of Nucleobases, Nucleosides, Nucleotides and Oligonucleotides
Authors: Favetta P. , Ayari M. G. , Agrofoglio L. A.
Published: April 2018

Modified nucleosides have become cornerstones of treatment for patients with cancer or viral infections. Moreover, they are excreted in the urine of cancer patients in high levels and are considered to be potential tumor biomarkers. ATP and its analogues play an important role in several functions of the cardiovascular system. Moreover, circulating nucleotides have therapeutic importance on the progression of metabolic disorders. Thus, their detection and quantization are important. To gain in selectivity, the design of artificial polymer receptors, so-called molecularly imprinted polymers (MIPs) that can selectively recognize nucleotide bases, has gained importance from the theoretical application point of view. We will initially review the articles that are interested in the development of MIPs for the recognition of nucleoside analogues. Then, the second part of the chapter will describe the work published on the use of MIPs in the field of separation techniques and sample pretreatment. The final part will summarize research where the MIP technology can improve the analytical selectivity of the sensors of all types.
Molecularly Imprinted Polymers: Providing Selectivity to Sample Preparation
Authors: Martín-Esteban Antonio
Published: April 2018

In spite of the huge development in analytical instrumentation, sample preparation is still considered the bottle-neck of the whole analytical process. Nowadays, several sample preparation techniques are available for the extraction and clean-up of target analytes from any kind of sample. However, these techniques suffer from a lack of selectivity, making the final determination of target analytes at the low concentration levels nowadays required difficult in most cases. In this regard, molecularly imprinted polymers (MIPs), synthetic tailor-made materials, are able to selectively bind a target molecule in preference to other closely related compounds, thus making them ideal materials to perform selective extractions. The incorporation of MIPs as sorbents in solid-phase extraction, so-called “molecularly imprinted solid-phase extraction” (MISPE), is already accepted in analytical laboratories and some MIPs (both in bulk and/or packed in cartridges) are commercially available. Besides, MIP incorporation to other sample preparation techniques, such as solid-phase microextraction (SPME), stir bar sorptive extraction (SBSE) or matrix solid-phase dispersion (MSPD), has been recently proposed and successfully applied to the extraction of different analytes from complex samples. Finally, the recent combination of MIPs with liquid membranes circumvents the traditional lack of recognition associated to MIPs in aqueous media thus opening new areas of application.
Facile deposition of Pt nanoparticles on Sb-doped SnO2 support with outstanding active surface area for the oxygen reduction reaction
Authors: Mohamed Rhiyaad , Binninger Tobias , Kooyman Patricia J. , Hoell Armin , Fabbri Emiliana , Patru Alexandra , Heinritz Adrian , Schmidt Thomas J. , Levecque Pieter
Published: April 2018

Synthesis of Sb–SnO2 supported Pt nanoparticles with an outstanding ECSA for the oxygen reduction reaction.
The synergistic effect of non-stoichiometry and Sb-doping on air-stable α-CsPbI3 for efficient carbon-based perovskite solar cells
Authors: Xiang Sisi , Li Weiping , Wei Ya , Liu Jiaming , Liu Huicong , Zhu Liqun , Chen Haining
Published: April 2018

Excess CsI and Sb-doping stabilize α-CsPbI3 at room temperature in an air atmosphere.