bluuebunny/crossref_metadata_2025 huggingface dataset:
Human trophoblast requires galectin-3 for cell migration and invasion
Authors: Bojić-Trbojević Ž. , Jovanović Krivokuća M. , Vilotić A. , Kolundžić N. , Stefanoska I. , Zetterberg F. , Nilsson U. J. , Leffler H. , Vićovac Lj.
Published: February 2019

Invasive extravillous cytotrophoblast of the human placenta expresses galectins-1, -3, and -8 in vivo and in vitro. This study aimed to investigate the potential role of galectin-3 in cell migration and invasion, using recombinant human galectin-3 (rhgalectin-3), small molecule galectin inhibitor I47, and galectin-3 silencing. HTR-8/SVneo cell migration was stimulated by rhgalectin-3 and reduced by I47, which could be neutralised by rhgalectin-3. Inhibitor specificity and selectivity for the galectins expressed in extravillous trophoblast were validated in solid phase assays using recombinant galectin-1, -3, -8, confirming selectivity for galectin-3. HTR-8/SVneo cell migration and invasion, and invasion by isolated trophoblast cells in primary culture were significantly reduced in the presence of I47, which could be restored by rhgalectin-3. Upon HTR-8/SVneo cell treatment with galectin-3 siRNA both LGALS3 and galectin-3 protein were dramatically decreased. Silencing of galectin-3 induced significant reduction in cell migration and invasion, which was restored by rhgalectin-3. The influence on known mediators of cell invasion, MMP2 and -9, and integrins α1, α5, and β1 was followed in silenced cells, showing lower levels of MMPs and a large reduction in integrin subunit β1. These results show that galectin-3 acts as a pro-invasive autocrine/paracrine factor in trophoblast in vitro.
MG132 protects against renal dysfunction by regulating Akt-mediated inflammation in diabetic nephropathy
Authors: Zeng Wei , Qi Wei , Mu Jiao , Wei Yi , Yang Li-Ling , Zhang Qian , Wu Qiong , Tang Jian-Ying , Feng Bing
Published: February 2019

Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD). To date, mounting evidence has shown that inflammation may contribute to the pathogenesis of DN. Recent reports have shown that proteasome inhibitors display cytoprotection by reducing the phosphorylation of Akt, a serine/threonine kinase, plays a critical role in cellular survival and metabolism and can crosstalk with inflammation. Therefore, we hypothesized that MG132, specific proteasome inhibitor, could provide renoprotection by suppressing Akt-mediated inflammation in DN. In vivo, male Sprague-Dawley rats were divided into normal control group (NC), diabetic nephropathy group (DN), DN model plus MG132 treatment group (MG132), and DN model plus deguelin treatment group (Deguelin)(deguelin, a specific inhibitor of Akt). In vitro, a human glomerular mesangial cell lines (HMCs) was exposed to 5.5 mmol/L glucose (CON), 30 mmol/L glucose (HG), 30 mmol/L glucose with 0.5 umol/L MG132 (MG132) and 30 mmol/L glucose with 5 umol/L deguelin (Deguelin). Compared with NC, DN showed a significant increase in the urinary protein excretion rate and inflammatory cytokines, as well as p-Akt. Compared with CON, HMCs co-cultured with HG was notably proliferated, which is in accord with α-smooth muscle actin (α-SMA) expression. These alterations were inhibited by administration of MG132 or deguelin. In conclusion, MG132 significantly inhibits the development of DN by regulating Akt phosphorylation-mediated inflammatory activation.
The development of white matter structural changes during the process of deterioration of the visual field
Authors: Hofstetter Shir , Sabbah Norman , Mohand-Saïd Saddek , Sahel José-Alain , Habas Christophe , Safran Avinoam B. , Amedi Amir
Published: February 2019

Emerging evidence suggests that white matter plasticity in the adult brain is preserved after sensory and behavioral modifications. However, little is known about the progression of structural changes during the process of decline in visual input. Here we studied two groups of patients suffering from advanced retinitis pigmentosa with specific deterioration of the visual field: patients who had lost their peripheral visual field, retaining only central (“tunnel”) vision, and blind patients with complete visual field loss. Testing of these homogeneous groups made it possible to assess the extent to which the white matter is affected by loss of partial visual input and whether partially preserved visual input suffices to sustain stability in tracts beyond the primary visual system. Our results showed gradual changes in diffusivity that are indicative of degenerative processes in the primary visual pathway comprising the optic tract and the optic radiation. Interestingly, changes were also found in tracts of the ventral stream and the corticospinal fasciculus, depicting a gradual reorganisation of these tracts consequentially to the gradual loss of visual field coverage (from intact perception to partial vision to complete blindness). This reorganisation may point to microstructural plasticity underlying adaptive behavior and cross-modal integration after partial visual deprivation.
Magnetic particle mapping using magnetoelectric sensors as an imaging modality
Authors: Friedrich Ron-Marco , Zabel Sebastian , Galka Andreas , Lukat Nils , Wagner Jan-Martin , Kirchhof Christine , Quandt Eckhard , McCord Jeffrey , Selhuber-Unkel Christine , Siniatchkin Michael , Faupel Franz
Published: February 2019

Magnetic nanoparticles (MNPs) are a hot topic in the field of medical life sciences, as they are highly relevant in diagnostic applications. In this regard, a large variety of novel imaging methods for MNP in biological systems have been invented. In this proof-of-concept study, a new and novel technique is explored, called Magnetic Particle Mapping (MPM), using resonant magnetoelectric (ME) sensors for the detection of MNPs that could prove to be a cheap and efficient way to localize the magnetic nanoparticles. The simple and straightforward setup and measurement procedure includes the detection of higher harmonic excitations of MNP ensembles. We show the feasibility of this approach by building a measurement setup particularly suited to exploit the inherent sensor properties. We measure the magnetic response from 2D MNP distributions and reconstruct the distribution by solving the inverse problem. Furthermore, biological samples with magnetically labeled cells were measured and reconstruction of the distribution was compared with light microscope images. Measurement results suggest that the approach presented here is promising for MNP localization.
On the mechanism behind the inverse melting in systems with competing interactions
Authors: Mendoza-Coto Alejandro , Nicolao Lucas , Díaz-Méndez Rogelio
Published: February 2019

The competition between a short range attractive interaction and a nonlocal repulsive interaction promote the appearance of modulated phases. In this work we present the microscopic mechanisms leading to the emergence of inverse transitions in such systems by considering a thorough mean-field analysis of a variety of minimal models with different competing interactions. We identify the specific connections between the characteristic energy of the homogeneous and modulated phases and the observed reentrant behaviors in the phase diagram. In particular, we find that reentrance is appreciable when the characteristic energy cost of the homogeneous and modulated phases are comparable to each other, and for systems in which the local order parameter is limited. In the asymptotic limit of high energy cost of the homogeneous phase we observe that the degree of reentrance decreases exponentially with the ratio of the characteristic energy cost of homogeneous and modulated phases. These mean-field results are confronted with Langevin simulations of an effective coarse grained model, confirming the expected extension of the reentrance in the phase diagram. These results shed new light on many systems undergoing inverse melting transitions by qualitatively improving the understanding of the interplay of entropy and energy around the inverse melting points.
Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188Re radionuclide for cancer therapy
Authors: Petriev V. M. , Tischenko V. K. , Mikhailovskaya A. A. , Popov A. A. , Tselikov G. , Zelepukin I. , Deyev S. M. , Kaprin A. D. , Ivanov S. , Timoshenko V. Yu. , Prasad P. N. , Zavestovskaya I. N. , Kabashin A. V.
Published: February 2019

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.
Negative reflection of elastic guided waves in chaotic and random scattering media
Authors: Gérardin Benoît , Laurent Jérôme , Legrand François , Prada Claire , Aubry Alexandre
Published: February 2019

The propagation of waves in complex media can be harnessed either by taming the incident wave-field impinging on the medium or by forcing waves along desired paths through its careful design. These two alternative strategies have given rise to fascinating concepts such as time reversal or negative refraction. Here, we show how these two processes are intimately linked through the negative reflection phenomenon. A negative reflecting mirror converts a wave of positive phase velocity into its negative counterpart and vice versa. In this article, we experimentally demonstrate this phenomenon with elastic waves in a 2D billiard and in a disordered plate by means of laser interferometry. Despite the complexity of such configurations, the negatively reflected wave field focuses back towards the initial source location, thereby mimicking a phase conjugation operation while being a fully passive process. The super-focusing capability of negative reflection is also highlighted in a monochromatic regime. The negative reflection phenomenon is not restricted to guided elastic waves since it can occur in zero-gap systems such as photonic crystals, chiral metamaterials or graphene. Negative reflection can thus become a tool of choice for the control of waves in all fields of wave physics.
Quantitative nontumorous and tumorous human brain tissue assessment using microstructural co- and cross-polarized optical coherence tomography
Authors: Yashin Konstantin S. , Kiseleva Elena B. , Moiseev Alexander A. , Kuznetsov Sergey S. , Timofeeva Lidia B. , Pavlova Nadezhda P. , Gelikonov Grigory V. , Medyanik Igor А. , Kravets Leonid Ya. , Zagaynova Elena V. , Gladkova Natalia D.
Published: February 2019

Optical coherence tomography (OCT) is a promising method for detecting cancer margins during tumor resection. This study focused on differentiating tumorous from nontumorous tissues in human brain tissues using cross-polarization OCT (CP OCT). The study was performed on fresh ex vivo human brain tissues from 30 patients with high- and low-grade gliomas. Different tissue types that neurosurgeons should clearly distinguish during surgery, such as the cortex, white matter, necrosis and tumorous tissue, were separately analyzed. Based on volumetric CP OCT data, tumorous and normal brain tissue were differentiated using two optical coefficients — attenuation and forward cross-scattering. Compared with white matter, tumorous tissue without necrotic areas had significantly lower optical attenuation and forward cross-scattering values. The presence of particular morphological patterns, such as necrosis and injured myelinated fibers, can lead to dramatic changes in coefficient values and create some difficulties in differentiating between tissues. Color-coded CP OCT maps based on optical coefficients provided a visual assessment of the tissue. This study demonstrated the high translational potential of CP OCT in differentiating tumorous tissue from white matter. The clinical use of CP OCT during surgery in patients with gliomas could increase the extent of tumor resection and improve overall and progression-free survival.
Intravitreal aflibercept and ranibizumab for pachychoroid neovasculopathy
Authors: Jung Byung Ju , Kim Joo Young , Lee Jae Hyung , Baek Jiwon , Lee Kook , Lee Won Ki
Published: February 2019

This retrospective study was to compare the efficacy of intravitreal injection of ranibizumab and aflibercept for patients with pachychoroid neovasculopathy. 54 eyes were initially treated with 3 monthly loading injections of ranibizumab or aflibercept. Treatment switching from ranibizumab to aflibercept, and aflibercept to photodynamic therapy was done at 3 months in case of incomplete fluid absorption. At 3 months, the rate of complete fluid absorption was significantly higher in the aflibercept-treated group than in the ranibizumab-treated group (82.6% vs 51.6%, p = 0.018). The mean reduction of subfoveal choroidal thickness was significantly greater in the aflibercept group than in the ranibizumab group (−35 µm vs −9 µm, p = 0.013). There was no significant difference between the two groups in terms of visual improvement or decrease in central macular thickness. Complete fluid absorption was achieved after switching from ranibizumab to aflibercept in 13 of 15 eyes (86.7%). Adjunctive photodynamic therapy was required in 6 eyes. In conclusion, treatment mainly with anti-vascular endothelial growth factor effectively improved visual acuity within 12 months (from 20/56 to 20/44 at 3 months and to 20/36 at 12 months). Aflibercept was superior to ranibizumab in achieving dry macula and reducing choroidal thickness at 3 months.
Autofluorescence is a Reliable in vitro Marker of Cellular Senescence in Human Mesenchymal Stromal Cells
Authors: Bertolo Alessandro , Baur Martin , Guerrero Julien , Pötzel Tobias , Stoyanov Jivko
Published: February 2019

Mesenchymal stromal cells (MSC) are used in cell therapies, however cellular senescence increases heterogeneity of cell populations and leads to uncertainty in therapies’ outcomes. The determination of cellular senescence is time consuming and logistically intensive. Here, we propose the use of endogenous autofluorescence as real-time quantification of cellular senescence in human MSC, based on label-free flow cytometry analysis. We correlated cell autofluorescence to senescence using senescence-associated beta-galactosidase assay (SA-β-Gal) with chromogenic (X-GAL) and fluorescent (C12FDG) substrates, gene expression of senescence markers (such as p16INK4A, p18INK4C, CCND2 and CDCA7) and telomere length. Autofluorescence was further correlated to MSC differentiation assays (adipogenesis, chondrogenesis and osteogenesis), MSC stemness markers (CD90/CD106) and cytokine secretion (IL-6 and MCP-1). Increased cell autofluorescence significantly correlated with increased SA-β-Gal signal (both X-GAL and C12FDG substrates), cell volume and cell granularity, IL-6/MCP-1 secretion and with increased p16INK4A and CCND2 gene expression. Increased cell autofluorescence was negatively associated with the expression of the CD90/CD106 markers, osteogenic and chondrogenic differentiation potentials and p18INK4C and CDCA7 gene expression. Cell autofluorescence correlated neither with telomere length nor with adipogenic differentiation potential. We conclude that autofluorescence can be used as fast and non-invasive senescence assay for comparing MSC populations under controlled culture conditions.
Oncogenic Y68 frame shift mutation of PTEN represents a mechanism of docetaxel resistance in endometrial cancer cell lines
Authors: Zhang Haiyang , Wang Song , Cacalano Nicholas , Zhu He , Liu Qiuju , Xie Michael , Kamrava Mitchell , Konecny Gottfried , Jin Shunzi
Published: February 2019

In this study, we aimed to identify mutations of key genes associated with docetaxel resistance in nine endometrial cancer cell lines. Endometrial cancers are associated with several critical gene mutations, including PIK3A, PTEN, and KRAS. Different gene mutations in endometrial cancer cells have varied responses to anticancer drugs and cancer therapies. The most frequently altered gene in endometrioid endometrial carcinoma tumors is PTEN. PTEN protein has lipid phosphatase and protein phosphatase activity, as well as other functions in the nucleus. Although the tumor-suppressive function of PTEN has mainly been attributed to its lipid phosphatase activity, a role for PTEN protein phosphatase activity in cell cycle regulation has also been suggested. Various tumor type-specific PTEN mutations are well documented. Here, nine endometrioid endometrial cancer cell lines with PIK3A, PTEN, and KRAS gene mutations were treated with docetaxel and radiation. One mutation with a docetaxel drug-resistant effect was a truncated form of PTEN. Among PTEN mutations in endometrial cancer cells, the Y68 frame shift mutation of PTEN constitutes a major mechanism of resistance to docetaxel treatment. The molecular mechanism involves truncation of the 403 amino acid PTEN protein at amino acid 68 by the Y68 frame shift, leading to the loss of PTEN protein phosphatase and lipid phosphatase activities.
Macrophage Migration Inhibitory Factor Acts as the Potential Target of a Newly Synthesized Compound, 1-(9′-methyl-3′-carbazole)-3, 4-dihydro-β-carboline
Authors: Ko Pin-Hao , Shen Ya-Ching , Murugan Kaliyappan , Huang Chiung-Wei , Sivakumar Govindan , Pal Pinki , Liao Chia-Ching , Luo Kai-Shin , Chuang Eric Y. , Tsai Mong-Hsun , Lai Liang-Chuan
Published: February 2019

For a newly synthesized compound, identifying its target protein is a slow but pivotal step toward understand its pharmacologic mechanism. In this study, we systemically synthesized novel manzamine derivatives and chose 1-(9′-methyl-3′-carbazole)-3, 4-dihydro-β-carboline (MCDC) as an example to identify its target protein and function. MCDC had potent toxicity against several cancer cells. To identify its target protein, we first used a docking screen to predict macrophage migration inhibitory factor (MIF) as the potential target. Biochemical experiments, including mutation analysis and hydrogen-deuterium exchange assays, validated the binding of MCDC to MIF. Furthermore, MCDC was shown by microarrays to interfere with the cell cycle of breast cancer MCF7 cells. The activated signaling pathways included AKT phosphorylation and S phase-related proteins. Our results showed MIF as a potential direct target of a newly synthesized manzamine derivative, MCDC, and its pharmacologic mechanisms.
Dissecting the current caesarean section rate in Shanghai, China
Authors: Ming Yanhong , Li Meng , Dai Fei , Huang Rong , Zhang Jinwen , Zhang Lin , Qin Ming , Zhu Liping , Yu Hongping , Zhang Jun
Published: February 2019

The high caesarean section (CS) rate has been of great public concern around the world. Yet, large-scale studies of dissecting such a high CS rate are few in the Chinese population. We carried out a cross-sectional survey randomly selecting 10,855 births from 20 hospitals in Shanghai from January to June, 2016. Labor and delivery information was extracted from medical records. The Robson classification system for CS was used to classify all women into ten groups. The overall CS rate was 41.5%. Prelabor CS in nulliparous, term singleton vertex women was the predominant contributor (37.4%) to the total CS and accounted for the second highest proportion of total births (15.5%) in all hospital types. The vast majority of women with a previous CS had a repeat CS (96.6%). CS rate was still high in Shanghai. Nulliparous women in low risk and having CS before labour, often without any medical indication, was a major contributor to the high CS rate.
Risk factors and clinical characteristics of Pneumocystis jirovecii pneumonia in lung cancer
Authors: Lee Eun Hye , Kim Eun Young , Lee Sang Hoon , Roh Yun Ho , Leem Ah Young , Song Joo Han , Kim Song Yee , Chung Kyung Soo , Jung Ji Ye , Kang Young Ae , Kim Young Sam , Chang Joon , Park Moo Suk
Published: February 2019

Solid malignancies are associated with the development of Pneumocystis jirovecii pneumonia (PJP). This study aimed to evaluate the risk factors for PJP among patients with lung cancer. This retrospective case-control study compared patients who had lung cancer with PJP (n = 112) or without PJP (n = 336) matched according to age, sex, histopathology, and stage. PJP definition was based on (i) positive PCR or direct immunofluorescence results for pneumocystis, (ii) clinical symptoms and radiological abnormalities that were consistent with a pneumonic process, and (iii) received targeted PJP treatment. The development of PJP was associated with radiotherapy (RTx), concurrent chemoradiotherapy (CCRTx), lymphopenia, and prolonged high-dose steroid therapy (20 mg of prednisolone equivalent per day for ≥3 weeks). Multivariate analysis revealed independent associations with prolonged high-dose steroid therapy (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.06–3.63; p = 0.032) and CCRTx (OR: 2.09, 95% CI: 1.27–3.43; p = 0.004). Steroid use was frequently related to RTx pneumonitis or esophagitis (29 patients, 43.3%). Prolonged high-dose steroid therapy and CCRTx were risk factors for PJP development among patients with lung cancer. As these patients had a poor prognosis, clinicians should consider PJP prophylaxis for high-risk patients with lung cancer.
Five genomic regions have a major impact on fat composition in Iberian pigs
Authors: Pena R. N. , Noguera J. L. , García-Santana M. J. , González E. , Tejeda J. F. , Ros-Freixedes R. , Ibáñez-Escriche N.
Published: February 2019

The adipogenic nature of the Iberian pig defines many quality attributes of its fresh meat and dry-cured products. The distinct varieties of Iberian pig exhibit great variability in the genetic parameters for fat deposition and composition in muscle. The aim of this work is to identify common and distinct genomic regions related to fatty acid composition in Retinto, Torbiscal, and Entrepelado Iberian varieties and their reciprocal crosses through a diallelic experiment. In this study, we performed GWAS using a high density SNP array on 382 pigs with the multimarker regression Bayes B method implemented in GenSel. A number of genomic regions showed strong associations with the percentage of saturated and unsaturated fatty acid in intramuscular fat. In particular, five regions with Bayes Factor >100 (SSC2 and SSC7) or >50 (SSC2 and SSC12) explained an important fraction of the genetic variance for miristic, palmitoleic, monounsaturated (>14%), oleic (>10%) and polyunsaturated (>5%) fatty acids. Six genes (RXRB, PSMB8, CHGA, ACACA, PLIN4, PLIN5) located in these regions have been investigated in relation to intramuscular composition variability in Iberian pigs, with two SNPs at the RXRB gene giving the most consistent results on oleic and monounsaturated fatty acid content.
Combination of Platelet expression of PKCepsilon and cardiac troponin-I for early diagnosis of chest pain patients in the emergency department
Authors: Carubbi Cecilia , Masselli Elena , Pozzi Giulia , Mattioli Maria , Martini Silvia , Goldoni Matteo , Aloe Rosalia , Cervellin Gianfranco , Vitale Marco , Gobbi Giuliana
Published: February 2019

A rapid differential diagnosis of the clinical conditions underlying chest pain is a relevant clinical issue. Specifically, a fast rule-in or -out of acute myocardial infarction (AMI) is mandatory to improve diagnostic outcome and cost-effectiveness of patient management. We demonstrated that Protein Kinase C (PKC) epsilon is selectively expressed by platelets from AMI patients, accounting for increased platelet activation. Thus, we hypothesized that PKCepsilon-expressing platelets may represent a pathophysiological marker of AMI that could be utilized in combination with troponin-I, the conventional marker of cardiac injury, to add diagnostic information in chest pain workup. In 94 chest pain patients consecutively admitted to Parma University Hospital, we tested the diagnostic performance of flow-cytometric detection of PKCepsilon expressing platelets in discriminating AMI vs. non-AMI conditions. We demonstrated that PKCepsilon-expressing platelets were significantly higher in patients with AMI. Flow cytometry detection of PKCepsilon-expressing platelets showed high sensitivity and specificity (87.5% and 84.4%, respectively) and good diagnostic accuracy (AUC: 0.875). The combination of PKCepsilon expressing platelets and cardiac troponin clearly discriminates patients with 100% and 0% of probability to be affected by AMI. Overall, we highlighted a dual marker strategy potentially useful for a rapid rule-in or -out of myocardial infarction in chest pain patients.
Juvenile hormone controls ovarian development in female Anopheles albimanus mosquitoes
Authors: Hernández-Martínez Salvador , Cardoso-Jaime Víctor , Nouzova Marcela , Michalkova Veronika , Ramirez Cesar E. , Fernandez-Lima Francisco , Noriega Fernando G.
Published: February 2019

Anophelinae mosquitoes are vectors of human malaria, a disease that infects hundreds of millions of people and causes almost 600,000 fatalities annually. Despite their medical importance, laboratory studies on key aspects of Anophelinae reproductive biology have been limited, and in particular, relatively little is known about the role of juvenile hormone (JH) in the control of female reproduction. The study presented here attempts to fill a gap of knowledge in our understanding of the JH control of ovarian development in female Anophelinae mosquitoes, using Anopheles albimanus as a model. Our studies revealed that JH controls the tempo of maturation of primary follicles in An. albimanus in a similar manner to that previously described in Aedes aegypti. At adult eclosion JH hemolymph titer was low, increased in 1-day old sugar-fed insects, and decreased in blood fed individuals. JH titers decreased if An. albimanus females were starved, and were reduced if insects emerged with low teneral reserves, precluding previtellogenic ovarian development. However, absolute hemolymph titers were lower than Ae. aegypti. Decapitation experiments suggested that if teneral reserves are sufficient, factors from the head activate JH synthesis by the corpora allata (CA) during the first 9–12 h after adult emergence. In conclusion, our studies support the hypothesis that JH controls previtellogenic ovarian development in female An. albimanus mosquitoes, in a similar manner that have been described in Culicinae.
Simultaneous Improvement in the Strength and Formability of Commercially Pure Titanium via Twinning-induced Crystallographic Texture Control
Authors: Won Jong Woo , Park Chan Hee , Hong Jaekeun , Lee Chong Soo , Hong Seong-Gu
Published: February 2019

The rolling texture formed in the conventional cold rolling process of commercially pure titanium (CP-Ti) for producing a metal sheet significantly limits the potential applications of CP-Ti sheets in various industrial sectors by impairing the formability. Here, we report that by exploiting a twinning-induced crystallographic texture modification, the rolling texture can be weakened and dispersed effectively, leading to a simultaneous improvement in the formability and yield strength. A two-stage cold rolling process was designed with intermediate annealing at a late stage of the conventional cold rolling process to generate deformation twins. The intermediate annealing drove the activation of $$\{11\bar{2}2\}$$
{
11

2
¯

2
}
twin and $$\{11\bar{2}2\}$$
{
11

2
¯

2
}
 – $$\{10\bar{1}2\}$$
{
10

1
¯

2
}
double twin in the second stage of the rolling process by removing the internal reaction stress developed in the first stage of the rolling process through recrystallization, and the crystallographic feature of the $$\{11\bar{2}2\}$$
{
11

2
¯

2
}
twinned region, i.e., $$\{11\bar{2}2\}$$
{
11

2
¯

2
}
twin texture, was effective for  type slips and $$\{10\bar{1}2\}$$
{
10

1
¯

2
}
twinning to accommodate a through-thickness strain as well as for reducing the planar anisotropy. This enhanced thinning capability and reduced planar anisotropy in the $$\{11\bar{2}2\}$$
{
11

2
¯

2
}
twin texture led to an improvement of the formability. We demonstrated the feasibility of the suggested two-stage cold rolling process with ASTM grade 2 CP-Ti.
Experimental proof of the reciprocal relation between spin Peltier and spin Seebeck effects in a bulk YIG/Pt bilayer
Authors: Sola Alessandro , Basso Vittorio , Kuepferling Michaela , Dubs Carsten , Pasquale Massimo
Published: February 2019

We verify for the first time the reciprocal relation between the spin Peltier and spin Seebeck effects in a bulk YIG/Pt bilayer. Both experiments are performed on the same YIG/Pt device by a setup able to accurately determine heat currents and to separate the spin Peltier heat from the Joule heat background. The sample-specific value for the characteristics of both effects measured on the present YIG/Pt bilayer is (6.2 ± 0.4) × 10−3 KA−1. In the paper we also discuss the relation of both effects with the intrinsic and extrinsic parameters of YIG and Pt and we envisage possible strategies to optimize spin Peltier refrigeration.
Three distinct regions of cRaf kinase domain interact with membrane
Authors: Prakash Priyanka , Hancock John F. , Gorfe Alemayehu A.
Published: February 2019

Raf kinases are downstream effectors of small GTPase Ras. Mutations in Ras and Raf are associated with a variety of cancers and genetic disorders. Of the three Raf isoforms, cRaf is most frequently involved in tumor initiation by Ras. Cytosolic Raf is auto-inhibited and becomes active upon recruitment to the plasma membrane. Since the catalytic domain of Raf is its kinase domain, we ask the following: does the kinase domain of Raf has potential to interact with membrane and if yes, what role does the membrane interaction play? We present a model of cRaf kinase domain in complex with a heterogeneous membrane bilayer using atomistic molecular dynamics simulation. We show that the kinase domain of cRaf has three distinct membrane-interacting regions: a polybasic motif (R.RKTR) from the regulatory αC-helix, an aromatic/hydrophobic cluster from the N-terminal acidic region (NtA) and positively charged/aromatic cluster from the activation segment (AS). We show that residues from these regions form an extended membrane-interacting surface that resembles the membrane-interacting residues from known membrane-binding domains. Activating phosphorylatable regions (NtA and AS), make direct contact with the membrane whereas R.RKTR forms specific multivalent salt bridges with PA. PA lipids dwell for longer times around the R.RKTR motif. Our results suggest that membrane interaction of monomeric cRaf kinase domain likely orchestrates the Raf activation process and modulates its function. We show that R.RKTR is a hotspot that interacts with membrane when cRaf is monomeric and becomes part of the interface upon Raf dimerization. We propose that in terms of utilizing a specific hotspot to form membrane interaction and dimer formation, both Raf and its upstream binding partner KRas, are similar.
Structural, luminescence and thermometric properties of nanocrystalline YVO4:Dy3+ temperature and concentration series
Authors: Kolesnikov I. E. , Kalinichev A. A. , Kurochkin M. A. , Golyeva E. V. , Terentyeva A. S. , Kolesnikov E. Yu. , Lähderanta E.
Published: February 2019

We report systematic study of Dy3+-doped YVO4 nanophosphors synthesized via modified Pechini technique. Effect of calcination temperature and doping concentration on structure and luminescence has been investigated. XRD and Raman spectroscopy revealed preparation of single phase nanoparticles without any impurities. Synthesized nanopowders consisted of weakly agglomerated nanoparticles with average size about 50 nm. Photoluminescence spectra of YVO4:Dy3+ nanoparticles consisted of the characteristic narrow lines attributed to the intra-configurational 4f-4f transitions dominating by the hypersensitive 4F9/2–6H13/2 transition. The calcination temperature variation did not affect 4F9/2 lifetime, whereas increase of doping concentration resulted in its gradual decline. Potential application of YVO4:Dy3+ 1 at.% and 2 at.% nanopowders as ratiometric luminescence thermometers within 298–673 K temperature range was tested. The main performances of thermometer including absolute and relative thermal sensitivities and temperature uncertainty were calculated. The maximum relative thermal sensitivity was determined to be 1.8% K−1@298 K, whereas the minimum temperature uncertainty was 2 K.
Reflection of treatment proficiency of hydroxyurea treated β-thalassemia serum samples through nuclear magnetic resonance based metabonomics
Authors: Khalid Ayesha , Siddiqui Amna Jabbar , Ansari Saqib Hussain , Musharraf Syed Ghulam
Published: February 2019

β-Thalassemia is a widespread autosomal recessive blood disorder found in most parts of the world. Fetal hemoglobin (HbF), a form of hemoglobin is found in infants, replaced by adult hemoglobin (HbA) after birth. Hydroxyurea (HU) is one of the most effective HbF inducer used for the treatment of anemic diseases. We aimed to improve the understanding of HU therapy in β-thalassemia by metabonomics approach using 1H NMR spectroscopy. This study includes 40 cases of β-thalassemia before and after HU therapy along with 40 healthy as controls. Carr-Purcell-Meiboom-Gill (CPMG) sequence was used to identify forty-one putative metabolites. Generation of models like partial least square discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) based on different metabolites including lipids, amino acids, glucose, fucose, isobutyrate, and glycerol revealed satisfactory outcomes with 85.2% and 91.1% classification rates, respectively. The concentration of these metabolites was altered in β-thalassemia samples. However, after HU treatment metabolic profile of same patients showed closeness towards healthy. Deviant metabolic pathways counting lipoprotein changes, glycolysis, TCA cycle, fatty acid and choline metabolisms were identified as having significant differences among study groups. Findings of this study may open a better way to monitor HU treatment effectiveness in β-thalassemia patients, as the results suggested that metabolic profile of β-thalassemia patients shows similarity towards normal profile after this therapy.
Sonication induced amorphisation in Ag nanowires
Authors: Dai Han , Li Haitao , Li Zhutie , Zhao Junfeng , Yu Xinxiang , Sun Jie , An Qi
Published: February 2019

It has long been conjectured that pure-element face-centred cubic (fcc) metals can be transformed into a glassy state by deformation at ultra-high strain rates. However, when an impact force is applied at the nanoscale, deformation-induced melting prevents observations of fcc metal amorphisation. Here we propose a sonication treatment of Ag nanowires (fcc) and confirmed amorphisation induced by high strain rates at bent areas of the Ag nanowires. Owing to the mismatch of the deformation modes between the core and the surface, we observed a diameter related increase of the ductility of Ag nanowires under deformation at ultra-high strain rates generated by sonication. The sonication-prepared amorphous Ag was stable at room temperature. Amorphous Ag at the bent areas was highly reactive and was readily recrystallized under light illumination or vulcanised. Our study verifies the occurrence of high strain rate induced amorphisation in pure fcc MGs and provides a powerful tool for mechanical studies on metal nanomaterials under extremely high strain rates and forces.
Synthesis and Characterization of Multiple-Cation Rb(MAFA)PbI3 Perovskite Single Crystals
Authors: Kim Hyojung , Byun Hye Ryung , Jeong Mun Seok
Published: February 2019

We synthesized multiple-cation Rb(MAFA)PbI3 perovskite single crystals for the first time. The effect of Rb+ substitution was systemically investigated, and the addition of 1.5 M 5% RbI was the optimum condition to obtain high-quality Rb(MAFA)PbI3 single crystals. Lattice shrinkage occurred in the Rb(MAFA)PbI3 single crystal because of the small ionic radius of Rb+, resulting in blue-shifted absorption and photoluminescence (PL) peaks. The 1.5 M 5% RbI-added (MAFA)PbI3 single crystal showed the longest carrier lifetime of 18.35 ns, exhibiting the highest photoresponse than other crystals. We believe that this work will provide a basic insight into the mixed-cation perovskite single crystals for the future optoelectronic applications.
Distinct Metabolic Endotype Mirroring Acute Respiratory Distress Syndrome (ARDS) Subphenotype and its Heterogeneous Biology
Authors: Viswan Akhila , Ghosh Pralay , Gupta Devendra , Azim Afzal , Sinha Neeraj
Published: February 2019

Predisposing aetiologies in Acute Respiratory Distress Syndrome (ARDS), perpetuates to heterogeneous clinical course hampering therapeutic response. Therefore, physiological variables need to be identified by stratifying ARDS subphenotypes and endotype, to target ARDS heterogeneity. The present study is stimulated by the fact that the ARDS heterogeneity arises from diverse pathophysiological changes leading to distinct ARDS endotypes characterized by perturbed biological mechanism which can be exploited in terms of metabolic profile by metabolomics. Biological endotypes using (n = 464 patients and controls), mBALF and serum samples were identified by high – resolution NMR spectroscopy from two clinically diagnosed ARDS subtypes grouped under mild, moderate and severe ARDS as subphenotype1and pulmonary and extra – pulmonary ARDS as subphenotype2. The identified mBALF endotypes (isoleucine, leucine, valine, lysine/arginine, tyrosine, threonine) and serum endotypes (proline, glutamate, phenylalanine, valine) in both subphenotypes by statistical analysis were tested for their reproducibility and robustness. By combining metabolic endotypes with clinical based mortality score (APACHE and SOFA) added to their predictive performance as ARDS mortality predictors. Thus, a comprehensive set of mBALF endotypes representing compartmentalized lung milieu and serological endotypes representing systemic markers of ARDS subtypes were validated. The interlinked biological pathway of these disease specific endotype further elucidated their role as candidate biomarker in governing ARDS heterogeneous biology.
Extremely robust photocurrent generation of titanium dioxide photoanodes bio-sensitized with recombinant microalgal light-harvesting proteins
Authors: Lämmermann Nina , Schmid-Michels Fabian , Weißmann Aike , Wobbe Lutz , Hütten Andreas , Kruse Olaf
Published: February 2019

Bio-dyes for light harvesting in dye-sensitized solar cells (DSSC) have the advantage of being environmentally-friendly, non-toxic alternatives, which can be produced in a sustainable fashion. Free photosynthetic pigments are unstable in the presence of light and oxygen, a situation which can hardly be avoided during the operation of DSSCs, especially in large-scale applications. We therefore investigated the recombinant light-harvesting protein LHCBM6, which naturally occurs in the photosynthetic apparatus of the green microalga Chlamydomonas reinhardtii as a bio-dye in DSSCs. Photocurrent densities of up to 0.87 and 0.94 mA·cm−2 were determined for the DSSCs and solar energy to electricity conversion efficiencies (η) reached about 0.3% (100 mW·cm−2; AM 1.5 G filter applied). Importantly, we observed an unprecedented stability of LHCII-based DSSCs within long DSSC operation times of at least 7 days in continuous light and show that operation times are restricted by electrolyte decomposition rather than reduced dye performance, as could be demonstrated by DSSC reactivation following re-supplementation with fresh electrolyte. To the best of our knowledge, this is the first study analysing bio-dye sensitized DSSCs over such long periods, which revealed that during illumination an activation of the DSSCs occurs.
Overlapping and differential functions of ATF6α versus ATF6β in the mouse heart
Authors: Correll Robert N. , Grimes Kelly M. , Prasad Vikram , Lynch Jeffrey M. , Khalil Hadi , Molkentin Jeffery D.
Published: February 2019

Hemodynamic stress on the mammalian heart results in compensatory hypertrophy and activation of the unfolded protein response through activating transcription factor 6α (ATF6α) in cardiac myocytes, but the roles of ATF6α or the related transcription factor ATF6β in regulating this hypertrophic response are not well-understood. Here we examined the effects of loss of ATF6α or ATF6β on the cardiac response to pressure overload. Mice gene-deleted for Atf6 or Atf6b were subjected to 2 weeks of transverse aortic constriction, and each showed a significant reduction in hypertrophy with reduced expression of endoplasmic reticulum (ER) stress-associated proteins compared with controls. However, with long-term pressure overload both Atf6 and Atf6b null mice showed enhanced decompensation typified by increased heart weight, pulmonary edema and reduced function compared to control mice. Our subsequent studies using cardiac-specific transgenic mice expressing the transcriptionally active N-terminus of ATF6α or ATF6β revealed that these factors control overlapping gene expression networks that include numerous ER protein chaperones and ER associated degradation components. This work reveals previously unappreciated roles for ATF6α and ATF6β in regulating the pressure overload induced cardiac hypertrophic response and in controlling the expression of genes that condition the ER during hemodynamic stress.
Selective Capture and Purification of MicroRNAs and Intracellular Proteins through Antisense-vectorized Magnetic Nanobeads
Authors: Gessner Isabel , Yu Xiaojie , Jüngst Christian , Klimpel Annika , Wang Lingyu , Fischer Thomas , Neundorf Ines , Schauss Astrid C. , Odenthal Margarete , Mathur Sanjay
Published: February 2019

MicroRNAs (miRNAs) are small non-coding nucleotides playing a crucial role in posttranscriptional expression and regulation of target genes in nearly all kinds of cells. In this study, we demonstrate a reliable and efficient capture and purification of miRNAs and intracellular proteins using magnetic nanoparticles functionalized with antisense oligonucleotides. For this purpose, a tumor suppressor miRNA (miR-198), deregulated in several human cancer types, was chosen as the model oligonucleotide. Magnetite nanoparticles carrying the complementary sequence of miR-198 (miR-198 antisense) on their surface were delivered into cells and subsequently used for the extracellular transport of miRNA and proteins. The successful capture of miR-198 was demonstrated by isolating RNA from magnetic nanoparticles followed by real-time PCR quantification. Our experimental data showed that antisense-coated particles captured 5-fold higher amounts of miR-198 when compared to the control nanoparticles. Moreover, several proteins that could play a significant role in miR-198 biogenesis were found attached to miR-198 conjugated nanoparticles and analyzed by mass spectrometry. Our findings demonstrate that a purpose-driven vectorization of magnetic nanobeads with target-specific recognition ligands is highly efficient in selectively transporting miRNA and disease-relevant proteins out of cells and could become a reliable and useful tool for future diagnostic, therapeutic and analytical applications.
CaMello-XR enables visualization and optogenetic control of Gq/11 signals and receptor trafficking in GPCR-specific domains
Authors: Eickelbeck Dennis , Karapinar Raziye , Jack Alexander , Suess Sandra T. , Barzan Ruxandra , Azimi Zohre , Surdin Tatjana , Grömmke Michelle , Mark Melanie D. , Gerwert Klaus , Jancke Dirk , Wahle Petra , Spoida Katharina , Herlitze Stefan
Published: February 2019

The signal specificity of G protein-coupled receptors (GPCRs) including serotonin receptors (5-HT-R) depends on the trafficking and localization of the GPCR within its subcellular signaling domain. Visualizing traffic-dependent GPCR signals in neurons is difficult, but important to understand the contribution of GPCRs to synaptic plasticity. We engineered CaMello (Ca2+-melanopsin-local-sensor) and CaMello-5HT2A for visualization of traffic-dependent Ca2+ signals in 5-HT2A-R domains. These constructs consist of the light-activated Gq/11 coupled melanopsin, mCherry and GCaMP6m for visualization of Ca2+ signals and receptor trafficking, and the 5-HT2A C-terminus for targeting into 5-HT2A-R domains. We show that the specific localization of the GPCR to its receptor domain drastically alters the dynamics and localization of the intracellular Ca2+ signals in different neuronal populations in vitro and in vivo. The CaMello method may be extended to every GPCR coupling to the Gq/11 pathway to help unravel new receptor-specific functions in respect to synaptic plasticity and GPCR localization.
In-cell clean-up pressurized liquid extraction for the analysis of brominated diphenyl ethers in sewage sludge by GC-NCI-MS
Authors: Zhang Qian , Liu Yuanyuan , Han Guilin , Liang Tao , Okoli Chukwunonso Peter
Published: February 2019

An automated and sensitive method based on in-cell clean-up pressurized liquid extraction (PLE) was developed and validated for the simultaneous determination of 14 brominated diphenyl ethers in sewage sludge samples.
Polyhedral oligosilsesquioxane tethered perylene diimide for application in optical limiting and rapid detection of fluoride ions
Authors: Gao Tian , Zhou Wen-Fa , Zhao Yang , Shen Lei , Chang Wen-Ying , Musendo Rodney-Kudzai , Chen Er-Qiang , Song Ying-Lin , Ren Xiang-Kui
Published: February 2019

Polyhedral oligosilsesquioxane tethered perylene diimide was designed and synthesized for application in optical limiting and rapid detection of F−.
On the prevalence of smooth polymorphs at the nanoscale: implications for pharmaceuticals
Authors: Belenguer Ana M. , Cruz-Cabeza Aurora J. , Lampronti Giulio I. , Sanders Jeremy K. M.
Published: February 2019

Ball mill neat grinding leads to smoother whereas liquid assisted grinding leads to rougher pharmaceutical forms.
Facile synthesis of highly luminescent lithium silicate nanocrystals with varying crystal structures and morphology
Authors: Eladgham Ebtesam H. , Demchenko Denis O. , Nakagawara Tanner A. , Özgür Ümit , Arachchige Indika U.
Published: February 2019

The colloidal synthesis of lithium silicate nanocrystals with varying morphology, composition, crystal structures, and high intensity visible luminescence is reported.
Investigating coordination flexibility of glycerophosphodiesterase (GpdQ) through interactions with mono-, di-, and triphosphoester (NPP, BNPP, GPE, and paraoxon) substrates
Authors: Sharma Gaurav , Hu Qiaoyu , Jayasinghe-Arachchige Vindi M. , Paul Thomas J. , Schenk Gerhard , Prabhakar Rajeev
Published: February 2019

Interactions of the catalytically active binuclear form of glycerophosphodiesterase (GpdQ) with chemically diverse substrates,i.e.phosphomono-, phosphodi-, and phosphotriester have been investigated using molecular dynamics (MD) simulations.
Modeling of type IV and V sigmoidal adsorption isotherms
Authors: Buttersack Christoph
Published: February 2019

Interpretation of type IV adsorption isotherms not by a composed but unified concept.