bluuebunny/crossref_metadata_2025 huggingface dataset:
Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency
Authors: Mathieu J. , Detraux D. , Kuppers D. , Wang Y. , Cavanaugh C. , Sidhu S. , Levy S. , Robitaille A. M. , Ferreccio A. , Bottorff T. , McAlister A. , Somasundaram L. , Artoni F. , Battle S. , Hawkins R. D. , Moon R. T. , Ware C. B. , Paddison P. J. , Ruohola-Baker H.
Published: February 2019

To reveal how cells exit human pluripotency, we designed a CRISPR-Cas9 screen exploiting the metabolic and epigenetic differences between naïve and primed pluripotent cells. We identify the tumor suppressor, Folliculin(FLCN) as a critical gene required for the exit from human pluripotency. Here we show that FLCN Knock-out (KO) hESCs maintain the naïve pluripotent state but cannot exit the state since the critical transcription factor TFE3 remains active in the nucleus. TFE3 targets up-regulated in FLCN KO exit assay are members of Wnt pathway and ESRRB. Treatment of FLCN KO hESC with a Wnt inhibitor, but not ESRRB/FLCN double mutant, rescues the cells, allowing the exit from the naïve state. Using co-immunoprecipitation and mass spectrometry analysis we identify unique FLCN binding partners. The interactions of FLCN with components of the mTOR pathway (mTORC1 and mTORC2) reveal a mechanism of FLCN function during exit from naïve pluripotency.
Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A
Authors: Körner Andreas , Schlegel Martin , Kaussen Torsten , Gudernatsch Verena , Hansmann Georg , Schumacher Timo , Giera Martin , Mirakaj Valbona
Published: February 2019

The bidirectional communication between the immune and nervous system is important in regulating immune responses. Here we show that the adrenergic nerves of sympathetic nervous system orchestrate inflammation resolution and regenerative programs by modulating repulsive guidance molecule A (RGM-A). In murine peritonitis, adrenergic nerves and RGM-A show bidirectional activation by stimulating the mutual expression and exhibit a higher potency for the cessation of neutrophil infiltration; this reduction is accompanied by increased pro-resolving monocyte or macrophage recruitment, polymorphonucleocyte clearance and specialized pro-resolving lipid mediators production at sites of injury. Chemical sympathectomy results in hyperinflammation and ineffective resolution in mice, while RGM-A treatments reverse these phenotypes. Signalling network analyses imply that RGM-A and β2AR agonist regulate monocyte activation by suppressing NF-κB activity but activating RICTOR and PI3K/AKT signalling. Our results thus illustrate the function of sympathetic nervous system and RGM-A in regulating resolution and tissue repair in a murine acute peritonitis model.
Ruthenium atomically dispersed in carbon outperforms platinum toward hydrogen evolution in alkaline media
Authors: Lu Bingzhang , Guo Lin , Wu Feng , Peng Yi , Lu Jia En , Smart Tyler J. , Wang Nan , Finfrock Y. Zou , Morris David , Zhang Peng , Li Ning , Gao Peng , Ping Yuan , Chen Shaowei
Published: February 2019

Hydrogen evolution reaction is an important process in electrochemical energy technologies. Herein, ruthenium and nitrogen codoped carbon nanowires are prepared as effective hydrogen evolution catalysts. The catalytic performance is markedly better than that of commercial platinum catalyst, with an overpotential of only −12 mV to reach the current density of 10 mV cm-2 in 1 M KOH and −47 mV in 0.1 M KOH. Comparisons with control experiments suggest that the remarkable activity is mainly ascribed to individual ruthenium atoms embedded within the carbon matrix, with minimal contributions from ruthenium nanoparticles. Consistent results are obtained in first-principles calculations, where RuCxNy moieties are found to show a much lower hydrogen binding energy than ruthenium nanoparticles, and a lower kinetic barrier for water dissociation than platinum. Among these, RuC2N2 stands out as the most active catalytic center, where both ruthenium and adjacent carbon atoms are the possible active sites.
Cryo-EM structure of the homohexameric T3SS ATPase-central stalk complex reveals rotary ATPase-like asymmetry
Authors: Majewski Dorothy D. , Worrall Liam J. , Hong Chuan , Atkinson Claire E. , Vuckovic Marija , Watanabe Nobuhiko , Yu Zhiheng , Strynadka Natalie C. J.
Published: February 2019

Many Gram-negative bacteria, including causative agents of dysentery, plague, and typhoid fever, rely on a type III secretion system – a multi-membrane spanning syringe-like apparatus – for their pathogenicity. The cytosolic ATPase complex of this injectisome is proposed to play an important role in energizing secretion events and substrate recognition. We present the 3.3 Å resolution cryo-EM structure of the enteropathogenic Escherichia coli ATPase EscN in complex with its central stalk EscO. The structure shows an asymmetric pore with different functional states captured in its six catalytic sites, details directly supporting a rotary catalytic mechanism analogous to that of the heterohexameric F1/V1-ATPases despite its homohexameric nature. Situated at the C-terminal opening of the EscN pore is one molecule of EscO, with primary interaction mediated through an electrostatic interface. The EscN-EscO structure provides significant atomic insights into how the ATPase contributes to type III secretion, including torque generation and binding of chaperone/substrate complexes.
Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping
Authors: Gidoni Moriah , Snir Omri , Peres Ayelet , Polak Pazit , Lindeman Ida , Mikocziova Ivana , Sarna Vikas Kumar , Lundin Knut E. A. , Clouser Christopher , Vigneault Francois , Collins Andrew M. , Sollid Ludvig M. , Yaari Gur
Published: February 2019

Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population. To test this method, we generated a multi-individual data set of naive B-cell repertoires, and found allele usage bias, as well as a mosaic, tiled pattern of deleted IGHD and IGHV genes. The inferred haplotypes may have clinical implications for genetic disease predispositions. Our findings expand the knowledge that can be extracted from antibody repertoire sequencing data.
Evolutionary highways to persistent bacterial infection
Authors: Bartell Jennifer A. , Sommer Lea M. , Haagensen Janus A. J. , Loch Anne , Espinosa Rocio , Molin Søren , Johansen Helle Krogh
Published: February 2019

Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, here we screen 8 infection-relevant phenotypes of 443 longitudinalPseudomonas aeruginosaisolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: (1) a 2–3 year timeline of rapid adaptation after colonization, (2) variant “naïve” and “adapted” states reflecting discordance between phenotypic and genetic adaptation, (3) adaptive trajectories leading to persistent infection via three distinct evolutionary modes, and (4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.
Emergence of the structure-directing role of f-orbital overlap-driven covalency
Authors: Lu Erli , Sajjad Saira , Berryman Victoria E. J. , Wooles Ashley J. , Kaltsoyannis Nikolas , Liddle Stephen T.
Published: February 2019

FEUDAL (f’s essentially unaffected, d’s accommodate ligands) is a longstanding bonding model in actinide chemistry, in which metal-ligand binding uses 6d-orbitals, with the 5f remaining non-bonding. The inverse-trans-influence (ITI) is a case where the model may break down, and it has been suggested that ionic and covalent effects work synergistically in the ITI. Here, we report an experimentally grounded computational study that quantitatively explores the ITI, and in particular the structure-directing role of f-orbital covalency. Strong donor ligands generate a cis-ligand-directing electrostatic potential (ESP) at the metal centre. When f-orbital participation, via overlap-driven covalency, becomes dominant via short actinide-element distances, this ionic ESP effect is overcome, favouring a trans-ligand-directed geometry. This study contradicts the accepted ITI paradigm in that here ionic and covalent effects work against each other, and suggests a clearly non-FEUDAL, structure-directing role for the f-orbitals.
Role of defects in determining the magnetic ground state of ytterbium titanate
Authors: Bowman D. F. , Cemal E. , Lehner T. , Wildes A. R. , Mangin-Thro L. , Nilsen G. J. , Gutmann M. J. , Voneshen D. J. , Prabhakaran D. , Boothroyd A. T. , Porter D. G. , Castelnovo C. , Refson K. , Goff J. P.
Published: February 2019

Pyrochlore systems are ideally suited to the exploration of geometrical frustration in three dimensions, and their rich phenomenology encompasses topological order and fractional excitations. Classical spin ices provide the first context in which it is possible to control emergent magnetic monopoles, and anisotropic exchange leads to even richer behaviour associated with large quantum fluctuations. Whether the magnetic ground state of Yb2Ti2O7 is a quantum spin liquid or a ferromagnetic phase induced by a Higgs transition appears to be sample dependent. Here we have determined the role of structural defects on the magnetic ground state via the diffuse scattering of neutrons. We find that oxygen vacancies stabilise the spin liquid phase and the stuffing of Ti sites by Yb suppresses it. Samples in which the oxygen vacancies have been eliminated by annealing in oxygen exhibit a transition to a ferromagnetic phase, and this is the true magnetic ground state.
Challenges to curing primary brain tumours
Authors: Aldape Kenneth , Brindle Kevin M. , Chesler Louis , Chopra Rajesh , Gajjar Amar , Gilbert Mark R. , Gottardo Nicholas , Gutmann David H. , Hargrave Darren , Holland Eric C. , Jones David T. W. , Joyce Johanna A. , Kearns Pamela , Kieran Mark W. , Mellinghoff Ingo K. , Merchant Melinda , Pfister Stefan M. , Pollard Steven M. , Ramaswamy Vijay , Rich Jeremy N. , Robinson Giles W. , Rowitch David H. , Sampson John H. , Taylor Michael D. , Workman Paul , Gilbertson Richard J.
Published: February 2019

Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment.
Molecular interaction of fibrinogen with zeolite nanoparticles
Authors: Derakhshankhah Hossein , Hosseini Atiyeh , Taghavi Fereshteh , Jafari Samira , Lotfabadi Alireza , Ejtehadi Mohammad Reza , Shahbazi Sahba , Fattahi Ali , Ghasemi Atiyeh , Barzegari Ebrahim , Evini Mina , Saboury Ali Akbar , Shahri Seyed Mehdi Kamali , Ghaemi Behnaz , Ng Eng-Poh , Awala Hussein , Omrani Fatemeh , Nabipour Iraj , Raoufi Mohammad , Dinarvand Rassoul , shahpasand Koorosh , Mintova Svetlana , Hajipour Mohammad Javad , Mahmoudi Morteza
Published: February 2019

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPsviastrong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ377–394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.
Surface Replication, Fidelity and Data Loss in Traditional Dental Microwear and Dental Microwear Texture Analysis
Authors: Mihlbachler Matthew C. , Foy Melissa , Beatty Brian L.
Published: February 2019

Dental microwear studies often analyze casts rather than original surfaces, although the information loss associated with reproduction is rarely considered. To investigate the sensitivity of high magnification (150x) microwear analysis to common surface replication materials and methods, we compared areal surface texture parameters (ISO 25178-2) and traditional microwear variables (pits and scratches) generated from teeth and casts of rat molars exposed to experimental diets involving hard and soft foods in which abrasive materials had been added. Although the data from the original and replicated surfaces were correlated, many significant differences were found between the resulting data of the casts and original teeth. Both areal surface texture parameters and traditional microwear variables showed diminished ability to discriminate between the eight diet treatments when casts were analyzed. When areal surface texture parameters and traditional microwear variables were combined into a single discriminant function analysis, the cast data and original data produced the most similar results. Microwear researchers tend to favor either texture analysis or traditional microwear methods, better results may be generated by combining them. Although surface textures were not accurately reproduced by the casts, they retained sufficient information to discriminate between microwear of the experimental diets to a degree similar to the original teeth.
A data-informatics method to quantitatively represent ternary eutectic microstructures
Authors: Sargin Irmak , Beckman Scott P.
Published: February 2019

Many of the useful properties of modern engineering materials are determined by the material’s microstructure. Controlling the microstructure requires an understanding of the complex dynamics underlying its evolution during processing. Investigating the thermal and mass transport phenomena responsible for a structure requires establishing a common language to quantitatively represent the microstructures being examined. Although such a common language exists for some of the simple structures, which has allowed these materials to be engineered, there has yet to be a method to represent complex systems, such as the ternary microstructures, which are important for many technologies. Here we show how stereological and data science methods can be combined to quantitatively represent ternary eutectic microstructures relative to a set of exemplars that span the stereological attribute space. Our method uniquely describes ternary eutectic microstructures, allowing images from different studies, with different compositions and processing histories, to be quantitatively compared. By overcoming this long-standing challenge, it becomes possible to begin to make progress toward a quantitatively predictive theory of ternary eutectic growth. We anticipate that the method of quantifying instances of an object relative to a set of exemplars spanning attribute-space will be broadly applied to classify materials structures, and may also find uses in other fields.
Multifunctional Paper-Based Analytical Device for In Situ Cultivation and Screening of Escherichia coli Infections
Authors: Noiphung Julaluk , Laiwattanapaisal Wanida
Published: February 2019

Point-of-care testing (POCT) for uropathogen detection and chemical screening has great benefits for the diagnosis of urinary tract infections (UTIs). The goal of this study was to develop a portable and inexpensive paper-based analytical device (PAD) for cultivating bacteria in situ and rapidly testing for nitrite on the same device. The PAD was fabricated using a wax printing technique to create a pattern on Whatman No. 1 filter paper, which was then combined with a cotton sheet to support bacterial growth. Nitrite detection was based on the principle of the Griess reaction, and a linear detection range of 0–1.6 mg/dL (R2 = 0.989) was obtained. Scanning electron microscopy (SEM) analysis demonstrated that the bacteria were able to grow and formed a cluster on the cellulose fibres within 2 hours. The enzyme β-glucuronidase, which is specifically produced by Escherichia coli, was able to convert the pre-immobilized 5-bromo-4-chloro-3-indolyl-β-D-glucuronide sodium salt (X-GlcA), a colourless substrate, generating a blue colour. Under optimum conditions, the proposed device allowed bacterial concentrations in the range of 104–107 colony forming units (CFU)/mL to be quantified within 6 hours. Moreover, the use of this device enables the identification of E. coli pathogens with selectivity in real urine samples. In conclusion, the PAD developed in this study for UTI screening provides a rapid, cost-effective diagnostic method for use in remote areas.
New insights into the pathogenicity of non-synonymous variants through multi-level analysis
Authors: Sun Hong , Yu Guangjun
Published: February 2019

Precise classification of non-synonymous single nucleotide variants (SNVs) is a fundamental goal of clinical genetics. Next-generation sequencing technology is effective for establishing the basis of genetic diseases. However, identification of variants that are causal for genetic diseases remains a challenge. We analyzed human non-synonymous SNVs from a multilevel perspective to characterize pathogenicity. We showed that computational tools, though each having its own strength and weakness, tend to be overly dependent on the degree of conservation. For the mutations at non-degenerate sites, the amino acid sites of pathogenic substitutions show a distinct distribution in the classes of protein domains compared with the sites of benign substitutions. Overlooked disease susceptibility of genes explains in part the failures of computational tools. The more pathogenic sites observed, the more likely the gene is expressed in a high abundance or in a high tissue-specific manner, and have a high node degree of protein-protein interaction. The destroyed functions due to some false-negative mutations may arise because of a reprieve from the epigenetic repressed state which shouldn’t happen in multiple biological conditions, instead of the defective protein. Our work adds more to our knowledge of non-synonymous SNVs’ pathogenicity, thus will benefit the field of clinical genetics.
Elucidation of the unique mutation spectrum of severe hearing loss in a Vietnamese pediatric population
Authors: Han Jae Joon , Nguyen Pham Dinh , Oh Doo-Yi , Han Jin Hee , Kim Ah-Reum , Kim Min Young , Park Hye-Rim , Tran Lam Huyen , Dung Nguyen Huu , Koo Ja-Won , Lee Jun Ho , Oh Seung Ha , Anh Vu Hoang , Choi Byung Yoon
Published: February 2019

The mutational spectrum of deafness in Indochina Peninsula, including Vietnam, remains mostly undetermined. This significantly hampers the progress toward establishing an effective genetic screening method and early customized rehabilitation modalities for hearing loss. In this study, we evaluated the genetic profile of severe-to-profound hearing loss in a Vietnamese pediatric population using a hierarchical genetic analysis protocol that screened 11 known deafness-causing variants, followed by massively parallel sequencing targeting 129 deafness-associated genes. Eighty-seven children with isolated severe-to-profound non-syndromic hearing loss without family history were included. The overall molecular diagnostic yield was estimated to be 31.7%. The mutational spectrum for severe-to-profound non-syndromic hearing loss in our Vietnamese population was unique: The most prevalent variants resided in the MYO15A gene (7.2%), followed by GJB2 (6.9%), MYO7A (5.5%), SLC26A4 (4.6%), TMC1 (1.8%), ESPN (1.8%), POU3F4 (1.8%), MYH14 (1.8%), EYA1 (1.8%), and MR-RNR1 (1.1%). The unique spectrum of causative genes in the Vietnamese deaf population was similar to that in the southern Chinese deaf population. It is our hope that the mutation spectrum provided here could aid in establishing an efficient protocol for genetic analysis of severe-to-profound hearing loss and a customized screening kit for the Vietnamese population.
The effects of crossing ethnic boundaries on the autonomic nervous system in Muslim and Jewish young women in Israel
Authors: Saadi Diana , Agay-Shay Keren , Tirosh Emanuel , Schnell Izhak
Published: February 2019

Exposure to alien inter-group environments can differently effect ethnic groups’ autonomous nervous system, measured by heart rate variability (HRV). Our aim was to evaluate the effect of crossing alien ethnic boundaries on heart rate variability in three selected types of environments. In a field experiment study, we test responses of 72 Muslim and Jewish women to exposure to alien ethnic environments. We measured their HRV in intra and inter-ethnic parks, town centers and residential neighborhoods in Arab and Jewish adjacent towns. The subjects stayed half an hour in each environment. Mixed models were used to evaluate the effects. The results show that for both groups more favorable HRV measurements were demonstrated in intra-ethnic environments as compared to their HRV once crossing ethnic boundaries. The strongest effect in frequency domain (LF/HF) in response to ethnic boundary crossing was observed in the park for Muslims (β:0.65, 95%CI: 0.60–0.70) and for Jews (β: 0.60, 95%CI: 0.57–0.63). Following the eruption of the uprising, the most significant increase in LF/HF in response to ethnic boundary crossing was demonstrated in parks (β: 0.66, 95%CI: 0.60–0.71). In conclusion, both groups are effected by boundary crossing but there are ethnic differences in the autonomic nervous system balance and in response to crossing alien ethnic boundaries. A further study is needed to understand the causes of these differences.
Selectively detecting toluene and benzaldehyde by two stable lanthanide–organic frameworks as luminescent probes
Authors: Che Xue-Jing , Hou Sheng-Li , Shi Ying , Yang Guo-Li , Hou Yin-Ling , Zhao Bin
Published: February 2019

Two stable lanthanide–organic frameworks as luminescent probes to sensitively detect for toluene and benzaldehyde through luminescent quenching.
The role of surface chemistry in serum protein corona-mediated cellular delivery and gene silencing with lipid nanoparticles
Authors: Chen Dongyu , Ganesh Shanthi , Wang Weimin , Amiji Mansoor
Published: February 2019

The distinct protein corona fingerprint on lipid nanoparticles of different surface characteristics affected cellular transfection and gene silencing.
Stretchable and transparent nanofiber-networked electrodes based on nanocomposites of polyurethane/reduced graphene oxide/silver nanoparticles with high dispersion and fused junctions
Authors: Choi Young-In , Hwang Byeong-Ung , Meeseepong Montri , Hanif Adeela , Ramasundaram Subramaniyan , Trung Tran Quang , Lee Nae-Eung
Published: February 2019

Stretchable and transparent nanofiber-networked electrode.
Heterogeneous hydrosilylation reaction catalysed by platinum complexes immobilized on bipyridine-periodic mesoporous organosilicas
Authors: Naganawa Yuki , Maegawa Yoshifumi , Guo Haiqing , Gholap Sandeep Suryabhan , Tanaka Shinji , Sato Kazuhiko , Inagaki Shinji , Nakajima Yumiko
Published: February 2019

A platinum complex immobilized on a bipyridine-periodic mesoporous organosilica (BPy-PMO) effectively catalysed the hydrosilylation reaction and showed good reusability without the loss of the product yield.
A series of new vanadium(iii) chalcogenido-antimonates: an unusual seven-coordinate nitro-selenidovanadium(iii) complex
Authors: Luo Hai-Ying , Zhou Jian , Zou Hua-Hong
Published: February 2019

This work provides a rare example of high coordination of a nitro-selenidovanadium(iii) complex with photocurrent response properties.
On water: iodine-mediated direct construction of 1,3-benzothiazines from ortho-alkynylanilines by regioselective 6-exo-dig cyclization
Authors: Saini Kapil Mohan , Saunthwal Rakesh K. , Kumar Shiv , Verma Akhilesh K.
Published: February 2019

Herein, we report the 6-exo-dig ring closure of ortho-alkynylanilines with readily available aroyl isothiocyanate.
Myosin Va interacts with the exosomal protein spermine synthase
Authors: Dolce Luciano G. , Silva-Junior Rui M. P. , Assis Leandro H. P. , Nascimento Andrey F. Z. , Araujo Jackeline S. , Meschede Ingrid P. , Espreafico Enilza M. , de Giuseppe Priscila O. , Murakami Mário T.
Published: February 2019

Myosin Va (MyoVa) is an actin-based molecular motor that plays key roles in the final stages of secretory pathways, including neurotransmitter release. Several studies have addressed how MyoVa coordinates the trafficking of secretory vesicles, but why this molecular motor is found in exosomes is still unclear. In this work, using a yeast two-hybrid screening system, we identified the direct interaction between the globular tail domain (GTD) of MyoVa and four protein components of exosomes: the WD repeat-containing protein 48 (WDR48), the cold shock domain-containing protein E1 (CSDE1), the tandem C2 domain-containing protein 1 (TC2N), and the enzyme spermine synthase (SMS). The interaction between the GTD of MyoVa and SMS was further validated in vitro and displayed a Kd in the low micromolar range (3.5 ± 0.5 µM). SMS localized together with MyoVa in cytoplasmic vesicles of breast cancer MCF-7 and neuroblastoma SH-SY5Y cell lines, known to produce exosomes. Moreover, MYO5A knockdown decreased the expression of SMS gene and rendered the distribution of SMS protein diffuse, supporting a role for MyoVa in SMS expression and targeting.
Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis
Authors: Yu Xuhua , Seow Huei Jiunn , Wang Hao , Anthony Desiree , Bozinovski Steven , Lin Lin , Ye Ji-Ming , Vlahos Ross
Published: February 2019

Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion, and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiates and drives the long-term progression of disease. In particular, there are no effective therapeutics that target neutrophilic inflammation in COPD, which is known to cause tissue damage by degranulation of a suite of proteolytic enzymes including neutrophil elastase (NE). Matrine, an alkaloid compound extracted from Sophora flavescens Ait, has well known anti-inflammatory activity. Therefore, the aim of the present study was to investigate whether matrine could inhibit CS-induced lung inflammation in mice. Matrine significantly reduced CS-induced bronchoalveolar lavage fluid (BALF) neutrophilia and NE activity in mice. The reduction in BALF neutrophils in CS-exposed mice by matrine was not due to reductions in pro-neutrophil cytokines/chemokines, but rather matrine’s ability to cause apoptosis of neutrophils, which we demonstrated ex vivo. Thus, our data suggest that matrine has anti-inflammatory actions that could be of therapeutic potential in treating CS-induced lung inflammation observed in COPD.
Simplified wrist‐worn heart rate sensor using microwave VCO
Authors: McFerran C. , McKernan A. , Buchanan N.B.
Published: February 2019

This Letter presents a novel, wrist‐worn heart rate sensor, which is comprised of only a passive resonator and a voltage controlled oscillator (VCO). It is clearly demonstrated that valid heart rate data can be extracted off the DC bias circuit of the VCO, making this sensor one of the simplest of its kind ever reported. Experimental results are shown for successful measurements of the user's heart rate when the VCO was tuned to 2.42 GHz, with a DC bias voltage fluctuation of up to 10 mV representing the heart rate. These results are in agreement with those taken using a commercial optical sensor based heart monitor.
Effect of temperature on flow electrification under dc electrical field
Authors: Gao Yuan , Li Feng , Lu Wu , Zhao Wenbin
Published: February 2019

An oil–pressboard insulation system has been built to simulate converter transformer turn‐to‐turn insulation structure. Streaming current in the oil was measured while applying high dc voltage on the insulation at different temperatures. Flow electrification was also researched at low flow velocity of 0.2 m/s and at high flow velocity of 1.2 m/s. The streaming current increases exponentially with temperature when the high dc voltage is not applied on the insulation. However, at the same temperature, the streaming current is much smaller than that with the dc voltage been applied. The streaming current is in an inverted U‐shaped development with the increase of temperature, when the insulation withstands the dc voltage. The peak value of the streaming current was observed at a lower temperature when the dc voltage is higher. A mathematic model has been developed to describe the electrification characteristics of insulation under the dc voltage.
Wireless transmission‐based brain shift compensation system
Authors: Zhang Chenxi , Dong Yuan
Published: February 2019

The brain deforms during neurosurgery, resulting in a decrease in the accuracy of the image guided neurosurgery system (IGNS). In this study, a wireless transmission‐based brain shift compensation system (WBSCS) is implemented. The system consists of a laser range scanner for acquiring a cortical surface, and a mobile workstation equipped with a brain deformation correction software platform. The brain tissue deformation correction software platform includes a three‐dimensional visualisation module, a calibration module, a brain tissue extraction module, a meshing module, a boundary condition acquisition module, a finite element calculation module, a preoperative image update module, and a communication module. The system exchanges data with the IGNS through wireless communication. The authors used five pigs to test the system. Results of experiments show that the system can compensate for brain deformation. It worked with IGNS to provide brain‐shift‐compensation‐based guidance, improving the accuracy of the IGNS.
Molekulargenetische Hochdurchsatzanalysen beim Urothelkarzinom – Möglichkeiten der klinischen Anwendung
Authors: Todenhöfer Tilman , Miernik Arkadiusz , Seiler Roland
Published: February 2019

Die Anwendung von Hochdurchsatzanalysen zur Identifizierung von molekularen Veränderungen von Tumorgewebe hat zu einer signifikanten Verbesserung des Verständnisses von der Biologie des Urothelkarzinoms geführt. Unter anderem im Rahmen des Cancer Genome Atlas Projektes (TCGA) konnten anhand Veränderungen des Genexpressionsprofils molekulare Subtypen mit unterschiedlichem biologischem Verhalten identifiziert werden. Das im Rahmen dieser Analysen gewonnene Wissen könnte durch gezielte Anwendungen zu einer deutlichen Veränderung des klinischen Managements von Patienten mit Urothelkarzinomen führen. Erste Daten deuten darauf hin, dass die Bestimmung des molekularen Subtyps für die Entscheidung für oder wider eine neoadjuvante Chemotherapie sinnvoll sein könnte. Weiterhin werden in klinischen Prüfungen aktuell Substanzen untersucht, deren Effekt auf Tumoren mit bestimmten genetischen Veränderungen beschränkt zu sein scheint. Die Identifizierung von bestimmten Mutationen in zirkulierender Tumor-DNA durch liquid biopsies bietet nicht nur die Möglichkeit, metastasierte Tumoren ohne Entnahme einer Gewebebiopsie zu charakterisieren, sondern könnte auch für die Nachsorge von Patienten mit Urothelkarzinom gezielt eingesetzt werden.
Inklusive Forschung: Validierung der Skala zur Allgemeinen Selbstwirksamkeitserwartung (SWE) in Leichter Sprache an einer Stichprobe von Schülerinnen und Schülern mit sonderpädagogischem Förderbedarf
Authors: Berger Uwe , Fehlinger Meike , Mühleck Julia , Wick Katharina , Schwager Susanne
Published: February 2019

Hintergrund Etwa 7% der Schülerinnen und Schüler in Deutschland haben einen sonderpädagogischen Förderbedarf (SPF). Damit einher geht eine allgemein verringerte soziale Teilhabe, mitbedingt durch ein vermindertes Sprachverständnis. Zum Bestreben nach gesellschaftlicher Inklusion gehört daher die Bereitstellung von Text-Informationen in Leichter Sprache. Da in der sozialwissenschaftlichen und klinischen Forschung schriftliche Befragungen eine wichtige Rolle spielen, trifft dies auch auf psychometrische Fragebögen zu.

Fragestellung Vergleich der psychometrischen Güte der Original-Skala zur Allgemeinen Selbstwirksamkeitserwartung (SWE) mit einer in Leichte Sprache übersetzten Version (SWE-LS) der Skala.

Methode Parallele Anwendung der beiden Versionen der SWE bei N=94 Schülerinnen und Schülern im Alter zwischen 12 und 19 Jahren mit SPF aus 7 Förderschulen in Thüringen. Im Rahmen von Item-Analysen wurden die interne Konsistenz beider Skalen und die konvergente Validität gemessen.

Ergebnisse Beide Skalen-Versionen erreichten eine zufriedenstellende interne Konsistenz (SWE: α=0,74, SWE-LS: α=0,78). Die Skalenmittelwerte unterscheiden sich jedoch signifikant. Die konvergente Validität liegt bei r=0,69, wobei 3 Items nicht signifikant korrelieren (−0, 010,21). Der Anteil fehlender Werte ist bei der originalen SWE mit 16% auf Personenebene und 6,7% auf Itemebene signifikant höher als bei der SWE-LS mit 3,2 bzw. 0,5%.

Diskussion Insgesamt weist die in Leichte Sprache übersetzte SWE-LS eine bessere psychometrische Güte auf als die Originalskala. Auch der niedrigere Anteil fehlender Werte spricht für den Einsatz der SWE-LS.

Schlussfolgerungen Die Übersetzung standardisierter Fragebogen in Leichte Sprache bietet die Möglichkeit, auch Gruppen von Befragten in die Forschung mit einbeziehen, die bislang ausgeschlossen wurden bzw. nur indirekt (über Bezugs- oder Betreuungspersonen) befragt wurden. Der Aufwand für die Übersetzung ist vergleichbar mit der Übersetzung in andere Sprachen. Bei Leichter Sprache ist jedoch eine Rückübersetzung und damit eine Absicherung der inhaltlichen Validität nicht möglich.
Mindfulness and Skills Based Distress Reduction in Oncology: Das Webbasierte Psychoonkologische Make It Training
Authors: Ringwald Johanna , Gerstner Lena , Junne Florian , Ziser Katrin , Schäffeler Norbert , Wallwiener Markus , Hautzinger Martin , Bäuerle Alexander , Brucker Sara , Zipfel Stephan , Teufel Martin
Published: February 2019

Eine bedürfnisorientierte psychoonkologische Unterstützung für Frauen, die an Brustkrebs erkrankt sind, ist v. a. in strukturschwachen Gebieten nicht genügend vorhanden. Moderne telemedizinische und webbasierte Angebote (eHealth) können einen wichtigen Mehrwert in der psychoonkologischen Versorgung darstellen, da sie im Rahmen des Selbstmanagements unabhängig von personellen Ressourcen, Zeit und Ort verfügbar sind. Bisher fehlen solche supportive psychoonkologische Angebote weitestgehend im deutschsprachigen Raum. Aus diesem Grund wurde ein psychoonkologisches Online-Programm entwickelt. Inhalte für die zeitgemäße webbasierte, bedürfnisorientierte, psychoonkologische Intervention wurden aus Literatur und eigenen Vorstudien entwickelt. Ein Manual für ein Skills- und Achtsamkeitstraining (Make It Training- Mindfulness and skills based distress reduction training in oncology) im Websetting wurde entworfen, programmiert und elektronisch umgesetzt. Diese Intervention beinhaltet insgesamt acht krankheitsbezogene Sitzungen mit Lehrvideos, Audiodateien, interaktiven Arbeitsblättern, persönlicher Skillsbox sowie daraus entstehendem Abschlussmaterial nach jeder Sitzung. Die hier vorgestellten Bausteine zur Psychoedukation und Vermittlung von verhaltenstherapeutischen Skills zu den Themen Emotionsmanagement, Ressourcen, Stressmanagement und Selbstzuwendung, sowie ein fortlaufendes Achtsamkeitsmodul wurden entwickelt. Eine Akzeptanzüberprüfung (N=35) ergab hohe Werte für Akzeptanz und Zufriedenheit seitens der Patientinnen. 87% der Patientinnen würden anderen betroffenen Frauen das Make It Training weiterempfehlen. Mit dem Make It Training steht ein Programm zur Verfügung, das effektive Bewältigungsstrategien und Fertigkeiten im Umgang mit psychischen Belastungen und Anforderungen, die durch eine Krebserkrankung entstehen, vermittelt. Das webbasierte psychoonkologische Selbstmanagementprogramm kann die Versorgung in einem gestuften Ansatz nicht zuletzt in strukturschwachen Regionen für Patienten mit onkologischen Erkrankungen verbessern.
No Connection between Long-Term Lithium Treatment and Antithyroid Antibodies
Authors: Kraszewska Agnieszka , Ziemnicka Katarzyna , Sowiński Jerzy , Ferensztajn-Rochowiak Ewa , Rybakowski Janusz K.
Published: February 2019

Introduction The studies on the effect of lithium treatment on antithyroid antibodies showed either a higher concentration of these antibodies in patients receiving lithium compared to those lithium-naive or no difference between these groups. In lithium-treated bipolar patients, some researchers pointed to an association between antithyroid antibodies and other features of thyroid dysfunction such as hypothyroidism and decrease of glomerular filtration rate.

Methods We compared antithyroid antibodies in 98 patients (30 male, 68 female) with bipolar disorder, aged 62±13 years, who received lithium for 19±10 years to 39 patients (12 male, 27 female), aged 57±10 years, who were never treated with lithium. The antibodies against thyroid peroxidase (TPOAb), against thyroglobulin (TGAb), and thyroid-stimulating hormone (TSH) receptors (TSHRAb) were estimated.

Results No difference in the percentages of antibodies occurrence was found between groups, although the concentrations of TGAb were higher in patients receiving lithium. In lithium-treated patients, the presence of TPOAb was associated with lower concentrations of free triiodothyronine and the presence of TGAb, with higher concentrations of TSH. In females, the levels of TGAb were associated with lower thyroid volume. The concentrations of TPOAb correlated positively with the duration of lithium therapy in males, and those of TPOAb and TGAb negatively, with such duration, in female patients.

Conclusion The results obtained showed no significant connection between long-term lithium treatment and antithyroid antibodies. In bipolar patients receiving lithium longitudinally, antithyroid antibodies can be associated with some indexes of thyroid function. However, they behave differently in male and female patients.
Anterior Median Skull Base Reconstruction Using a Vascularized Free Flap: Rationale, Patient Selection and Outcome
Authors: Ungar Omer J. , Abergel Avraham , Safadi Ahmad , Zaretzki Arik , Yanko-Arzi Ravit , Fliss Dan M.
Published: February 2019

Objectives To present our method of median anterior skull base (ASB) reconstruction using a subcranial approach with a free flap in cases of naso-fronto-orbital (NFO) bony segment failure and in patients at high risk for future failure of the bony frontal segment.

Design This study presents as a retrospective case series.

Setting Tertiary university-affiliated medical center.

Participants Adult and pediatric patients who underwent median ASB resection via the subcranial approach with a free flap reconstruction were participated in this study.

Main Outcome Measures Pathologic outcome and postoperative quality of life (QoL) as assessed by a validated Hebrew version of the “Anterior Skull Base Quality-of-Life Questionnaire.”

Results The departmental database yielded 13 suitable patients aged between 15 and 70 years. The main indication (n = 7) for ASB surgery was osteoradionecrosis (ORN) of the NFO bony segment which was first detected at an average of 3.6 years (range: 2–32 years) postradiation therapy. High-risk patients for future ORN of the NFO segment (n = 3) were primarily reconstructed using a vascularized free flap. Nine patients had malignant disease, and four of them were alive without evidence of disease during the follow-up period (average, 48 months). Their QoL was comparable to that of patients who had undergone subcranial ASB resection without free flap reconstruction.

Conclusions The ASB median free flap method of reconstruction is a safe and reliable in cases of large complex median ASB defects without orbital resection or maxillectomy. This approach is suitable for patients who had undergone previous surgery, radiotherapy and/or those who present with osteoradionecrosis, as well as for patients with high risk of NFO segment ORN.
Applying Fibrin Glue under Pleurography for Intractable Secondary Spontaneous Pneumothorax
Authors: Cho Jeong Su , Ahn Hyo Yeong , Kim Yeong Dae , I. Hoseok , Eom Jung Seop
Published: February 2019

Background Prolonged air leakage is a problem that can frequently develop in patients with a secondary spontaneous pneumothorax (SSP) or in those who undergo thoracic surgery. However, the management of an air leak is difficult and reoperation might be avoided due to several reasons including adhesions. Herein, we introduce a fibrin glue application under pleurography (FGAP) and short-term outcomes in patients who underwent this procedure.

Methods FGAP was performed in 20 patients with an intractable persistent air leakage who had poor lung function, comorbidities to undergo general anesthesia and were expected severe adhesions due to previous surgery. All medical records were retrospectively reviewed.

Results Eighteen cases sealed soon after dropping the glue. One patient had a prolonged air leak for 12 days and another patient required an operation to control air leakage 16 days after the procedure. The mean duration of postoperative drainage was 4.17 ± 2.11 days (range: 3–14 days). No postprocedural complications were recorded. The mean duration of follow-up was 12.01 ± 5.02 months (range: 4–22 months).

Conclusion FGAP could be a treatment option to seal air leaks, especially in cases with intractable air leakage.
Obstetric Outcomes in Young Women with Breast Cancer: Prior, Postpartum, and Subsequent Pregnancies
Authors: Ma Kimberly K. , Preusse Courtney J. , Stevenson Philip A. , Winget Veronica L. , McDougall Jean A. , Li Christopher I. , Gadi Vijayakrishna K. , Gammill Hilary S.
Published: February 2019

Objective This study aimed to describe obstetric outcomes in a large cohort of young women with breast cancer, considering the chronological relationship of pregnancies with breast cancer diagnosis.

Study Design From a population-based cohort study of young women with breast cancer from 2004 to 2010, we conducted secondary interviews to obtain detailed obstetric histories. Pregnancies were categorized based on timing of breast cancer diagnosis: prior, postpartum, and subsequent pregnancies after breast cancer diagnosis. A generalized estimated equation model was used to account for correlated data.

Results In this cohort (n = 366), median age at breast cancer diagnosis was 40.1 years, and 84.7% were Caucasian. Tumor type was notable for 25.1% triple negative, and 56.1% had Stage I disease. There were 922 prior pregnancies, 21 with postpartum diagnosis of breast cancer, and 24 pregnancies subsequent to breast cancer diagnosis. Non-live birth outcomes occurred significantly more often in the postpartum group (p-value: 0.001) compared with the other groups, which had higher live birth rates, after adjustment for maternal age, parity, body mass index, and race.

Conclusion Overall, pregnancy outcomes before and after breast cancer diagnosis are reassuring.
Better understanding the onset of turbulence approaching Mach 5
Authors: Marchand Mark
Published: February 2019

New research seeks keys to better design approaches for hypersonic vehicles.
Distinction and characterisation of rice genotypes tolerant to combined stresses of salinity and partial submergence, proved by a high-resolution chlorophyll fluorescence imaging system
Authors: Pradhan Bhubaneswar , Chakraborty Koushik , Prusty Nibedita , Deepa  , Mukherjee Arup Kumar , Chattopadhyay Krishnendu , Sarkar Ramani Kumar
Published: February 2019

Chlorophyll a fluorescence (ChlF) parameters measured with fluorescence imaging techniques were used to investigate the combined effect of salt and partial submergence stress to understand photosynthetic performance in rice (Oryza sativa L.). ChlF parameters such as maximal fluorescence (Fm), variable fluorescence (Fv=Fm –F0), the maximal photochemical efficiency of PSII (Fv/Fm) and the quantum yield of nonregulated energy dissipation of PSII (Y(NO)) were able to distinguish genotypes precisely based on their sensitivity to stress. Upon analysis, we found the images of F0 were indistinguishable among the genotypes, irrespective of their tolerance to salt and partial submergence stress. On the contrary, the images of Fm and Fv/Fm showed marked differences between the tolerant and susceptible genotypes in terms of tissue greenness and the appearance of dark spots as stress symptoms. The images of effective PSII quantum yield, the coefficient of nonphotochemical quenching (qN) and the coefficient of photochemical quenching (qP) captured under different PAR were able to distinguish the tolerant and susceptible genotypes, and were also quite effective for differentiating the tolerant and moderately tolerant ones. Similarly, the values of electron transport rate, qN, qP and Y(NO) were also able to distinguish the genotypes based on their sensitivity to stress. Overall, this investigation indicates the suitability of chlorophyll fluorescence imaging technique for precise phenotyping of rice based on their sensitivity to the combined effect of salt and partial submergence.