bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes in two patients with vocal fold palsy who underwent revision arytenoid adduction surgery
Authors: Matsushima K , Matsui H , Ohira S , Matsuura K
Published: October 2019

Objective

This study investigated the position of adduction thread attachment, pulling direction and fixation position in revision arytenoid adduction surgery performed in two patients with left vocal fold palsy in whom satisfactory speech improvement had not been obtained by arytenoid adduction and type 1 thyroplasty.

Methods

Revision arytenoid adduction surgery was performed with the vocal fold in the midline position in both cases. A type 1 thyroplasty procedure was subsequently added in one case because of worsened quality of speech following arytenoid adduction.

Results and conclusion

Although the arytenoid adduction procedure is conceptually well established, there is still room for debate concerning the actual surgical procedures used. The technique described in this report is effective, suggesting that it is worthy of recognition as an index procedure.
How non-stationary are moderately supercritical shocks?
Authors: Gedalin Michael
Published: October 2019

Ion motion in a collisionless shock front is affected by macroscopic large-scale weakly varying and microscopic small-scale fast varying magnetic and electric fields. With the increase of the Mach number the role of the microscopic field is expected to become progressively more important. Using a combination of hybrid simulations and test particle analysis, we show that in moderately supercritical shocks macroscopic fields play the main role in ion motion across the shock. Pressure balance across the shock is only weakly broken and non-stationarity is related to the deviations from the total pressure from the constant value.
Diagnosis of spotted fever groupRickettsiainfections: the Asian perspective
Authors: Robinson Matthew T. , Satjanadumrong Jaruwan , Hughes Tom , Stenos John , Blacksell Stuart D.
Published: October 2019

Spotted fever group rickettsiae (SFG) are a neglected group of bacteria, belonging to the genusRickettsia, that represent a large number of new and emerging infectious diseases with a worldwide distribution. The diseases are zoonotic and are transmitted by arthropod vectors, mainly ticks, fleas and mites, to hosts such as wild animals. Domesticated animals and humans are accidental hosts. In Asia, local people in endemic areas as well as travellers to these regions are at high risk of infection. In this review we compare SFG molecular and serological diagnostic methods and discuss their limitations. While there is a large range of molecular diagnostics and serological assays, both approaches have limitations and a positive result is dependent on the timing of sample collection. There is an increasing need for less expensive and easy-to-use diagnostic tests. However, despite many tests being available, their lack of suitability for use in resource-limited regions is of concern, as many require technical expertise, expensive equipment and reagents. In addition, many existing diagnostic tests still require rigorous validation in the regions and populations where these tests may be used, in particular to establish coherent and worthwhile cut-offs. It is likely that the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem. If the specimen is collected early enough in the infection there will be no antibodies but there will be a greater chance of a PCR positive result. Conversely, when there are detectable antibodies it is less likely that there will be a positive PCR result. It is therefore extremely important that a complete medical history is provided especially the number of days of fever prior to sample collection. More effort is required to develop and validate SFG diagnostics and those of other rickettsial infections.
Sometimes Defence is Just an Excuse: Fortification Walls of the Southern Levantine Early Bronze Age
Authors: Ashkenazi Hai
Published: October 2019

The Early Bronze Age (EBA) of the southern Levant was the first period in which many sites became fortified. This process reached its climax during the latter part of the period (namely Early Bronze III). Until recently, most scholars saw this phenomenon as an indication that the period was characterized by a high level of organized conflict. The following article analyses the fortifications of eight EBA sites, as well as other markers of warfare, and argues that the period's fortifications were not as tactically efficient as they seem. Furthermore, other markers of war are generally missing. It seems that the period's fortifications were built mainly to demonstrate a town's might and power while deterring potential attackers. Taking into account the rise of social complexity during the period, they were also used to consolidate the society through the construction process and possibly to control movement and serve as a boundary marker. Incipient leaders, who planned and coordinated the construction, used possible threats and the construction process to aggrandize themselves as being the ‘protectors’ of the settlement.
Monuments to Enemies? ‘Rajput’ Statues in Mughal Capitals
Authors: VANINA EUGENIA
Published: October 2019

Various descriptions of the two Mughal capitals, Agra and Delhi, mention the gates of both royal forts as decorated with the statues of two warriors mounted on elephants. The list of those who had described these sculptures and reconstructed their history includes late-medieval Indian writers, European travellers to the Mughal empire, scholars from the nineteenth century onwards, authors of tourist guides; there is a popular oral narrative on them as well. The most widely spread version attributes the statues to the Rajput warriors who defended Chittor against the Mughal invasion and who were immortalised by the emperor Akbar in a sign of his recognition of their valour. This article is an attempt to ‘investigate’ the controversial story of a Mughal ruler glorifying his sworn enemies and to analyse historical circumstances that could be a background for such a narrative.
ON BORWEIN’S CONJECTURES FOR PLANAR UNIFORM RANDOM WALKS
Authors: ZHOU YAJUN
Published: October 2019

Let $p_{n}(x)=\int _{0}^{\infty }J_{0}(xt)[J_{0}(t)]^{n}xt\,dt$ be Kluyver’s probability density for $n$-step uniform random walks in the Euclidean plane. Through connection to a similar problem in two-dimensional quantum field theory, we evaluate the third-order derivative $p_{5}^{\prime \prime \prime }(0^{+})$ in closed form, thereby giving a new proof for a conjecture of J. M. Borwein. By further analogies to Feynman diagrams in quantum field theory, we demonstrate that $p_{n}(x),0\leq x\leq 1$ admits a uniformly convergent Maclaurin expansion for all odd integers $n\geq 5$, thus settling another conjecture of Borwein.
Compositional Specification in Rewriting Logic
Authors: MARTÍN ÓSCAR , VERDEJO ALBERTO , MARTÍ-OLIET NARCISO
Published: October 2019

Rewriting logic is naturally concurrent: several subterms of the state term can be rewritten simultaneously. But state terms are global, which makes compositionality difficult to achieve. Compositionality here means being able to decompose a complex system into its functional components and code each as an isolated and encapsulated system. Our goal is to help bringing compositionality to system specification in rewriting logic. The base of our proposal is the operation that we call synchronous composition. We discuss the motivations and implications of our proposal, formalize it for rewriting logic and also for transition structures, to be used as semantics, and show the power of our approach with some examples.
Investigation of a 256‐Monopole Transmit Antenna Array for Over‐the‐Horizon Radar in Canada
Authors: Henault Simon , Riddolls Ryan J.
Published: October 2019

A 256‐monopole planar array is investigated as a potential transmit antenna covering the entire 3‐ to 18‐MHz band in an over‐the‐horizon radar (OTHR) operating at high latitudes in Canada. This array is relatively inexpensive, simple to build, and offers the azimuth and elevation resolutions necessary to defeat the auroral clutter which has traditionally limited the operation of OTHR at high latitudes. It is demonstrated that excellent clutter rejection ratios are possible with this antenna array and accurate calibration, but significant performance degradation occurs with calibration errors in particular in the lower portion of the operating frequency band. Various calibration approaches and error mechanisms are studied. A new approach combining multiple‐input‐multiple‐output (MIMO) radar techniques at lower frequencies and conventional transmit null steering at higher frequencies is proposed and evaluated. This approach enhances the robustness of the array to calibration errors while preserving the radar unambiguous range‐Doppler space across the operating frequency band.
Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK
Authors: Li Sen , Zhang Yan , Sun Yewu , Zhang Guangzhen , Bai Jie , Guo Jianfei , Su Xudong , Du Hongquan , Cao Xi , Yang Jinkui , Wang Ting
Published: October 2019

Background

Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored.

Methods

We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-α)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation.

Results

We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-α-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK).

Conclusion

Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.
Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway
Authors: Liang Yu , Hou Lidan , Li Linjing , Li Lei , Zhu Liming , Wang Yu , Huang Xin , Hou Yichao , Zhu Danxi , Zou Huimin , Gu Yan , Weng Xiaoling , Wang Yingying , Li Yue , Wu Tianqi , Yao Mengfei , Gross Isabelle , Gaiddon Christian , Luo Meng , Wang Jianhua , Meng Xiangjun
Published: October 2019

The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose metabolism, similar to the effects of PDK2 knockdown. In addition, overexpression of PDK2 partially reversed the inhibitory effect of miR-149-3p on glucose metabolism. Finally, both DCA treatment and miR-149-3p overexpression in 5-FU-resistant CRC cells were found to markedly sensitize the chemotherapeutic effect of 5-FU in vivo, and this effect was also validated in a small retrospective cohort of CRC patients. Taken together, we determined that the p53/miR-149-3p/PDK2 signaling pathway can potentially be targeted with DCA treatment to overcome chemoresistant CRC.
Rev-erbα inhibits proliferation by reducing glycolytic flux and pentose phosphate pathway in human gastric cancer cells
Authors: Tao Linlin , Yu Haoyuan , Liang Rui , Jia Ru , Wang Jingjing , Jiang Kai , Wang Zhengguang
Published: October 2019

Rev-erbα is a nuclear receptor, which regulates circadian rhythm, inflammatory responses and lipid metabolism. We previously showed Rev-erbα reduction in human gastric cancer, which is associated with TMN stages and poor prognosis. We hypothesized that Rev-erbα modulates proliferation via glycolytic flux and the pentose phosphate pathway (PPP) in gastric cancer. Knockdown of Rev-erbα significantly increased proliferation as well as glycolytic flux and the PPP in human gastric cancer cells. These effects were reduced by a Rev-erbα agonist GSK4112 in a dose-dependent manner. Furthermore, Rev-erbα was recruited on the promoters of PFKFB3 and G6PD genes, thereby inhibiting their gene transcription. GSK4112 treatment reduced PFKFB3 and G6PD gene expression, which was not affected by BMAL1 knockdown. Pharmacological inhibition of glycolysis and the PPP using corresponding PFKFB3 and G6PD inhibitors attenuated Rev-erbα knockdown-induced proliferation in gastric cancer cells. GSK4112 treatment was not able to reduce proliferation in SGC-7901 overexpressing both PFKFB3 and G6PD genes. Both PFKFB3 and G6PD were overexpressed in patients with gastric cancer, and positively correlated with the TMN stages. The PPP and glycolysis were enhanced in gastric cancer tissues of patients with low expression of Rev-erbα compared to the patients with high expression of Rev-erbα. In conclusion, Rev-erbα reduction causes gastric cancer progression by augmenting the PPP and glycolysis.
Epigenetic signatures of smoking associate with cognitive function, brain structure, and mental and physical health outcomes in the Lothian Birth Cohort 1936
Authors: Corley Janie , Cox Simon R. , Harris Sarah E. , Hernandez Maria Valdéz , Maniega Susana Muñoz , Bastin Mark E. , Wardlaw Joanna M. , Starr John M. , Marioni Riccardo E. , Deary Ian J.
Published: October 2019

Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from self-reported (phenotypic) smoking measures. Blood DNA methylation levels were measured in 895 adults aged 70 years in the Lothian Birth Cohort 1936 (LBC1936) study using the Illumina 450K assay. A DNA methylation score based on 230 CpGs was used as a proxy for smoking exposure. Associations between smoking variables and health outcomes at age 70 were modelled using general linear modelling (ANCOVA) and logistic regression. Additional analyses of smoking with brain MRI measures at age 73 (n = 532) were performed. Smoking-DNAm scores were positively associated with self-reported smoking status (P < 0.001, eta-squared ɳ2 = 0.63) and smoking pack years (r = 0.69, P < 0.001). Higher smoking DNAm scores were associated with variables related to poorer cognitive function, structural brain integrity, physical health, and psychosocial health. Compared with phenotypic smoking, the methylation marker provided stronger associations with all of the cognitive function scores, especially visuospatial ability (P < 0.001, partial eta-squared ɳp2 = 0.022) and processing speed (P < 0.001, ɳp2 = 0.030); inflammatory markers (all P < 0.001, ranges from ɳp2 = 0.021 to 0.030); dietary patterns (healthy diet (P < 0.001, ɳp2 = 0.052) and traditional diet (P < 0.001, ɳp2 = 0.032); stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96); mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and at age 73; with MRI volumetric measures (all P < 0.001, ranges from ɳp2 = 0.030 to 0.052). Additionally, education was the most important life-course predictor of lifetime smoking tested. Our results suggest that a smoking-associated methylation biomarker typically explains a greater proportion of the variance in some smoking-related morbidities in older adults, than phenotypic measures of smoking exposure, with some of the accounted-for variance being independent of phenotypic smoking status.
Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders
Authors: Skogstrand Kristin , Hagen Christian Munch , Borbye-Lorenzen Nis , Christiansen Michael , Bybjerg-Grauholm Jonas , Bækvad-Hansen Marie , Werge Thomas , Børglum Anders , Mors Ole , Nordentoft Merethe , Mortensen Preben Bo , Hougaard David Michael
Published: October 2019

Mental disorders have for the majority of cases an unknown etiology, but several studies indicate that neurodevelopmental changes happen in utero or early after birth. We performed a nested case–control study of the relation between blood levels of neuro-developmental (S100B, BDNF, and VEGF-A) and inflammatory (MCP-1, TARC, IL-8, IL-18, CRP, and IgA) biomarkers in newborns, and later development of autism spectrum disorders (ASD, N = 751), attention deficit hyperactivity disorders (ADHD, N = 801), schizophrenia (N = 1969), affective (N = 641) or bipolar disorders (N = 641). Samples and controls were obtained as part of the iPSYCH Danish Case–Cohort Study using dried blood spot samples collected between 1981 and 2004, and stored frozen at the Danish National Biobank. In newborns lower blood level of BDNF was significantly associated with increased odds (OR 1.15) of developing ASD (p = 0.001). This difference could not be explained by genetic variation in the BDNF coding gene region. A tendency of decreased levels of all the neurotrophic markers and increased levels of all inflammatory markers was noted. The low newborn blood levels of BDNF in children developing ASD is an important finding, suggesting that lower BDNF levels in newborns contributes to the etiology of ASD and indicates new directions for further research. It may also help identifying a long-sought marker for high-ASD risk in, e.g., younger siblings of ASD children.
Precocious myelination in a mouse model of autism
Authors: Khanbabaei Maryam , Hughes Elizabeth , Ellegood Jacob , Qiu Lily R. , Yip Raven , Dobry Jenna , Murari Kartikeya , Lerch Jason P. , Rho Jong M. , Cheng Ning
Published: October 2019

Autism spectrum disorder (ASD) has been hypothesized to be a result of altered connectivity in the brain. Recent imaging studies suggest accelerated maturation of the white matter in young children with ASD, with underlying mechanisms unknown. Myelin is an integral part of the white matter and critical for connectivity; however, its role in ASD remains largely unclear. Here, we investigated myelin development in a model of idiopathic ASD, the BTBR mice. Magnetic resonance imaging revealed that fiber tracts in the frontal brain of the BTBR mice had increased volume at postnatal day 6, but the difference reduced over time, reminiscent of the findings in young patients. We further identified that myelination in the frontal brain of both male and female neonatal BTBR mice was increased, associated with elevated levels of myelin basic protein. However, myelin pattern was unaltered in adult BTBR mice, revealing accelerated developmental trajectory of myelination. Consistently, we found that signaling of platelet-derived growth factor receptor alpha (PDGFRα) was reduced in the frontal brain of neonatal BTBR mice. However, levels of microRNA species known to regulate PDGFRα signaling and myelination were unaltered. Together, these results suggest that precocious myelination could potentially contribute to increased volume and connectivity of the white matter observed in young children with ASD.
The oncometabolite 2-hydroxyglutarate produced by mutant IDH1 sensitizes cells to ferroptosis
Authors: Wang Tian-Xiang , Liang Jun-Yun , Zhang Cheng , Xiong Yue , Guan Kun-Liang , Yuan Hai-Xin
Published: October 2019

Ferroptosis is a non-apoptotic form of cell death characterized by the iron-dependent lipid peroxidation and is implicated in several human pathologies, such as tissue ischemia, neurodegeneration, and cancer. Ferroptosis appears to be high cell-context dependent and the regulation of ferroptosis by physiological or pathological conditions are unclear. Here, we report that tumor-derived IDH1 mutation sensitizes cells to ferroptosis. Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. Conversely, ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-HG promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4), a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Our results uncover a new role of mutant IDH1 and 2-HG in ferroptosis.
Author Correction: Local Josephson vortex generation and manipulation with a Magnetic Force Microscope
Authors: Dremov Viacheslav V. , Grebenchuk Sergey Yu. , Shishkin Andrey G. , Baranov Denis S. , Hovhannisyan Razmik A. , Skryabina Olga V. , Lebedev Nickolay , Golovchanskiy Igor A. , Chichkov Vladimir I. , Brun Christophe , Cren Tristan , Krasnov Vladimir M. , Golubov Alexander A. , Roditchev Dimitri , Stolyarov Vasily S.
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Organic sulfur was integral to the Archean sulfur cycle
Authors: Fakhraee Mojtaba , Katsev Sergei
Published: October 2019

The chemistry of the Early Earth is widely inferred from the elemental and isotopic compositions of sulfidic sedimentary rocks, which are presumed to have formed globally through the reduction of seawater sulfate or locally from hydrothermally supplied sulfide. Here we argue that, in the anoxic Archean oceans, pyrite could form in the absence of ambient sulfate from organic sulfur contained within living cells. Sulfides could be produced through mineralization of reduced sulfur compounds or reduction of organic-sourced sulfite. Reactive transport modeling suggests that, for sulfate concentrations up to tens of micromolar, organic sulfur would have supported 20 to 100% of sedimentary pyrite precipitation and up to 75% of microbial sulfur reduction. The results offer an alternative explanation for the low range of δ34S in Archean sulfides, and raise a possibility that sulfate scarcity delayed the evolution of dissimilatory sulfate reduction until the initial ocean oxygenation around 2.7 Ga.
Disorder compensation controls doping efficiency in organic semiconductors
Authors: Fediai Artem , Symalla Franz , Friederich Pascal , Wenzel Wolfgang
Published: October 2019

Conductivity doping of inorganic and organic semiconductors enables a fantastic variety of highly-efficient electronic devices. While well understood for inorganic materials, the mechanism of doping-induced conductivity and Fermi level shift in organic semiconductors remains elusive. In microscopic simulations with full treatment of many-body Coulomb effects, we reproduce the Fermi level shift in agreement with experimental observations. We find that the additional disorder introduced by doping can actually compensate the intrinsic disorder of the material, such that the total disorder remains constant or is even reduced at doping molar ratios relevant to experiment. In addition to the established dependence of the doping-induced states on the Coulomb interaction in the ionized host-dopant pair, we find that the position of the Fermi level and electrical conductivity is controlled by disorder compensation. By providing a quantitative model for doping in organic semiconductors we enable the predictive design of more efficient redox pairs.
Author Correction: Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor
Authors: Eftekharzadeh Bahareh , Banduseela Varuna C. , Chiesa Giulio , Martínez-Cristóbal Paula , Rauch Jennifer N. , Nath Samir R. , Schwarz Daniel M. C. , Shao Hao , Marin-Argany Marta , Di Sanza Claudio , Giorgetti Elisa , Yu Zhigang , Pierattelli Roberta , Felli Isabella C. , Brun-Heath Isabelle , García Jesús , Nebreda Ángel R. , Gestwicki Jason E. , Lieberman Andrew P. , Salvatella Xavier
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Task-evoked Negative BOLD Response and Functional Connectivity in the Default Mode Network are Representative of Two Overlapping but Separate Neurophysiological Processes
Authors: Parker David B. , Razlighi Qolamreza R.
Published: October 2019

The topography of the default mode network (DMN) can be obtained with one of two different functional magnetic resonance imaging (fMRI) methods: either from the spontaneous but organized synchrony of the low-frequency fluctuations in resting-state fMRI (rs-fMRI), known as “functional connectivity”, or from the consistent and robust deactivations in task-based fMRI (tb-fMRI), here referred to as the “negative BOLD response” (NBR). These two methods are fundamentally different, but their results are often used interchangeably to describe the brain’s resting-state, baseline, or intrinsic activity. While the DMN was initially defined by consistent task-based decreases in blood flow in a set of specific brain regions using PET imaging, recently nearly all studies on the DMN employ functional connectivity in rs-fMRI. In this study, we first show the high level of spatial overlap between NBR and functional connectivity of the DMN extracted from the same tb-fMRI scan; then, we demonstrate that the NBR in putative DMN regions can be significantly altered without causing any change in their overlapping functional connectivity. Furthermore, we present evidence that in the DMN, the NBR is more closely related to task performance than the functional connectivity. We conclude that the NBR and functional connectivity of the DMN reflect two separate but overlapping neurophysiological processes, and thus should be differentiated in studies investigating brain-behavior relationships in both healthy and diseased populations. Our findings further raise the possibility that the macro-scale networks of the human brain might internally exhibit a hierarchical functional architecture.
Structural analysis of fungal pathogenicity-related casein kinase α subunit, Cka1, in the human fungal pathogen Cryptococcus neoformans
Authors: Ong Belinda X. , Yoo Youngki , Han Myeong Gil , Park Jun Bae , Choi Myung Kyung , Choi Yeseul , Shin Jeon-Soo , Bahn Yong-Sun , Cho Hyun-Soo
Published: October 2019

CK2α is a constitutively active and highly conserved serine/threonine protein kinase that is involved in the regulation of key cellular metabolic pathways and associated with a variety of tumours and cancers. The most well-known CK2α inhibitor is the human clinical trial candidate CX-4945, which has recently shown to exhibit not only anti-cancer, but also anti-fungal properties. This prompted us to work on the CK2α orthologue, Cka1, from the pathogenic fungus Cryptococcus neoformans, which causes life-threatening systemic cryptococcosis and meningoencephalitis mainly in immunocompromised individuals. At present, treatment of cryptococcosis remains a challenge due to limited anti-cryptococcal therapeutic strategies. Hence, expanding therapeutic options for the treatment of the disease is highly clinically relevant. Herein, we report the structures of Cka1-AMPPNP-Mg2+ (2.40 Å) and Cka1-CX-4945 (2.09 Å). Structural comparisons of Cka1-AMPPNP-Mg2+ with other orthologues revealed the dynamic architecture of the N-lobe across species. This may explain for the difference in binding affinities and deviations in protein-inhibitor interactions between Cka1-CX-4945 and human CK2α-CX-4945. Supporting it, in vitro kinase assay demonstrated that CX-4945 inhibited human CK2α much more efficiently than Cka1. Our results provide structural insights into the design of more selective inhibitors against Cka1.
Shiga toxin signals via ATP and its effect is blocked by purinergic receptor antagonism
Authors: Johansson Karl E. , Ståhl Anne-Lie , Arvidsson Ida , Loos Sebastian , Tontanahal Ashmita , Rebetz Johan , Chromek Milan , Kristoffersson Ann-Charlotte , Johannes Ludger , Karpman Diana
Published: October 2019

Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli (EHEC), that cause gastrointestinal infection leading to hemolytic uremic syndrome. The aim of this study was to investigate if Stx signals via ATP and if blockade of purinergic receptors could be protective. Stx induced ATP release from HeLa cells and in a mouse model. Toxin induced rapid calcium influx into HeLa cells, as well as platelets, and a P2X1 receptor antagonist, NF449, abolished this effect. Likewise, the P2X antagonist suramin blocked calcium influx in Hela cells. NF449 did not affect toxin intracellular retrograde transport, however, cells pre-treated with NF449 exhibited significantly higher viability after exposure to Stx for 24 hours, compared to untreated cells. NF449 protected HeLa cells from protein synthesis inhibition and from Stx-induced apoptosis, assayed by caspase 3/7 activity. The latter effect was confirmed by P2X1 receptor silencing. Stx induced the release of toxin-positive HeLa cell- and platelet-derived microvesicles, detected by flow cytometry, an effect significantly reduced by NF449 or suramin. Suramin decreased microvesicle levels in mice injected with Stx or inoculated with Stx-producing EHEC. Taken together, we describe a novel mechanism of Stx-mediated cellular injury associated with ATP signaling and inhibited by P2X receptor blockade.
Population recovery changes population composition at a major southern Caribbean juvenile developmental habitat for the green turtle, Chelonia mydas
Authors: van der Zee Jurjan P. , Christianen Marjolijn J. A. , Nava Mabel , Velez-Zuazo Ximena , Hao Wensi , Bérubé Martine , van Lavieren Hanneke , Hiwat Michael , Berzins Rachel , Chevalier Johan , Chevallier Damien , Lankester Marie-Clélia , Bjorndal Karen A. , Bolten Alan B. , Becking Leontine E. , Palsbøll Per J.
Published: October 2019

Understanding the population composition and dynamics of migratory megafauna at key developmental habitats is critical for conservation and management. The present study investigated whether differential recovery of Caribbean green turtle (Chelonia mydas) rookeries influenced population composition at a major juvenile feeding ground in the southern Caribbean (Lac Bay, Bonaire, Caribbean Netherlands) using genetic and demographic analyses. Genetic divergence indicated a strong temporal shift in population composition between 2006–2007 and 2015–2016 (ϕST = 0.101, P < 0.001). Juvenile recruitment (<75.0 cm straight carapace length; SCL) from the north-western Caribbean increased from 12% to 38% while recruitment from the eastern Caribbean region decreased from 46% to 20% between 2006–2007 and 2015–2016. Furthermore, the product of the population growth rate and adult female abundance was a significant predictor for population composition in 2015–2016. Our results may reflect early warning signals of declining reproductive output at eastern Caribbean rookeries, potential displacement effects of smaller rookeries by larger rookeries, and advocate for genetic monitoring as a useful method for monitoring trends in juvenile megafauna. Furthermore, these findings underline the need for adequate conservation of juvenile developmental habitats and a deeper understanding of the interactions between megafaunal population dynamics in different habitats.
Radiotherapy-Compatible Robotic System for Multi-Landmark Positioning in Head and Neck Cancer Treatments
Authors: Ostyn Mark , Wang Siqiu , Kim Yun-Soung , Kim Siyong , Yeo Woon-Hong
Published: October 2019

The spine flexibility creates one of the most significant challenges to proper positioning in radiation therapy of head and neck cancers. Even though existing immobilization techniques can reduce the positioning uncertainty, residual errors (2–3 mm along the cervical spine) cannot be mitigated by single translation-based approaches. Here, we introduce a fully radiotherapy-compatible electro-mechanical robotic system, capable of positioning a patient’s head with submillimeter accuracy in clinically acceptable spatial constraints. Key mechanical components, designed by finite element analysis, are fabricated with 3D printing and a cyclic loading test of the printed materials captures a great mechanical robustness. Measured attenuation of most printed components is lower than analytic estimations and radiographic imaging shows no visible artifacts, implying full radio-compatibility. The new system evaluates the positioning accuracy with an anthropomorphic skeletal phantom and optical tracking system, which shows a minimal residual error (0.7 ± 0.3 mm). This device also offers an accurate assessment of the post correction error of aligning individual regions when the head and body are individually positioned. Collectively, the radiotherapy-compatible robotic system enables multi-landmark setup to align the head and body independently and accurately for radiation treatment, which will significantly reduce the need for large margins in the lower neck.
A Novel Optical Method To Reversibly Control Enzymatic Activity Based On Photoacids
Authors: Kagel Heike , Bier Frank F. , Frohme Marcus , Glökler Jörn F.
Published: October 2019

Most biochemical reactions depend on the pH value of the aqueous environment and some are strongly favoured to occur in an acidic environment. A non-invasive control of pH to tightly regulate such reactions with defined start and end points is a highly desirable feature in certain applications, but has proven difficult to achieve so far. We report a novel optical approach to reversibly control a typical biochemical reaction by changing the pH and using acid phosphatase as a model enzyme. The reversible photoacid G-acid functions as a proton donor, changing the pH rapidly and reversibly by using high power UV LEDs as an illumination source in our experimental setup. The reaction can be tightly controlled by simply switching the light on and off and should be applicable to a wide range of other enzymatic reactions, thus enabling miniaturization and parallelization through non-invasive optical means.
Super-Resolution Scanning Transmission X-Ray Imaging Using Single Biconcave Parabolic Refractive Lens Array
Authors: Mamyrbayev T. , Ikematsu K. , Meyer P. , Ershov A. , Momose A. , Mohr J.
Published: October 2019

A new super resolution imaging technique which potentially enables sub-µm spatial resolution, using a detector of pixels much larger than the spatial resolution, is proposed. The method utilizes sample scanning through a large number of identical X-ray microprobes periodically spaced (the period corresponds to a multiple of the pixel size), which reduces drastically the scanning time. The information about the sample illuminated by the microprobes is stored by large detector pixels. Using these data and sample position information, a super-resolution image reconstruction is performed. With a one-dimensional (1D) high aspect ratio nickel single lens array designed for theoretically expected sub-µm microprobes at 17 keV and fabricated by deep X-ray lithography and electroforming technique, 2 µm X-ray microprobes with a period of 10 µm were achieved. We performed a first experiment at KARA synchrotron facility, and it was demonstrated that the smallest structure of a test pattern with a size of 1.5 µm could be easily resolved by using images generated from a detector having a pixel size of 10.4 µm. This new approach has a great potential for providing a new microscopic imaging modality with a large field of view and short scan time.
Crosstalk between protein N-glycosylation and lipid metabolism in Saccharomyces cerevisiae
Authors: William James Antonisamy , Ravi Chidambaram , Srinivasan Malathi , Nachiappan Vasanthi
Published: October 2019

The endoplasmic reticulum (ER) is a multi functional organelle and plays a crucial role in protein folding and lipid biosynthesis. The SEC59 gene encodes dolichol kinase, required for protein glycosylation in the ER. The mutation of sec59-1 caused a protein N-glycosylation defect mediated ER stress resulting in increased levels of phospholipid, neutral lipid and sterol, whereas growth was reduced. In the sec59-1∆ cell, the N-glycosylation of vacuolar carboxy peptidase-Y (CPY) was significantly reduced; whereas the ER stress marker Kar2p and unfolded protein response (UPR) were significantly increased. Increased levels of Triacylglycerol (TAG), sterol ester (SE), and lipid droplets (LD) could be attributed to up-regulation of DPP1, LRO1, and ARE2 in the sec 59-1∆ cell. Also, the diacylglycerol (DAG), sterol (STE), and free fatty acids (FFA) levels were significantly increased, whereas the genes involved in peroxisome biogenesis and Pex3-EGFP levels were reduced when compared to the wild-type. The microarray data also revealed increased expression of genes involved in phospholipid, TAG, fatty acid, sterol synthesis, and phospholipid transport resulting in dysregulation of lipid homeostasis in the sec59-1∆ cell. We conclude that SEC59 dependent N-glycosylation is required for lipid homeostasis, peroxisome biogenesis, and ER protein quality control.
Short-Term Effects of Kinesio Taping in the Treatment of Latent and Active Upper Trapezius Trigger Points: two Prospective, Randomized, Sham-Controlled Trials
Authors: Noguera-Iturbe Yolanda , Martínez-Gramage Javier , Montañez-Aguilera Francisco Javier , Casaña José , Lisón Juan Francisco
Published: October 2019

The presence of myofascial trigger points (MTrPs) is one of the most common causes of musculoskeletal problems and may lead to limited professional activity. Among the various treatment methods proposed for MTrPs, Kinesio Taping (KT) is a non-invasive, painless, and less time-consuming method with fewer side effects that has become widely used as a therapeutic tool in a variety of prevention and rehabilitation protocols. The aim of the study was to evaluate the immediate and short-term efficacy of the space correction KT technique in patients with latent or active MTrPs in the upper trapezius muscle. Two parallel randomized sham-controlled trials were simultaneously executed: in trial A, ninety-seven participants with latent MTrPs were randomly assigned to either the KT (n = 51) or sham (n = 46) group; in trial B, thirty-seven participants with active MTrPs were assigned to the KT (n = 20) or sham (n = 17) group. The primary outcome was pressure pain threshold (PPT) in the upper trapezius muscle, measured with algometry. Secondary outcomes included the active range of motion (ROM) of the cervical spine (lateral flexion and rotation), measured with a cervical ROM goniometer. In each trial, two-way ANOVA tests were used to compare the study effects on the outcome measures between the groups, with time serving as the intra-group factor (baseline, immediately, and 72 h after the application) and the intervention type (KT and sham) as the between-group factor. At 72 h, participants receiving KT did not show significant differences in PPT (trial A: mean difference −1.8 N; 95% CI: [−8.1, 4.4], trial B: mean difference −1.2 N; 95% CI: [−7.4, 5.1]), cervical lateral flexion (trial A: mean difference 0.2 degrees; 95% CI: [−2.7, 3.1], trial B: mean difference −2.4 degrees; 95% CI: [−8.4, 3.6]), and cervical rotation (trial A: mean difference 3.7 degrees; 95% CI: [−0.1, 7.5], trial B: mean difference 1.4 degrees; 95% CI: [−5.7, 8.4]), compared to the sham groups. Thus, the results of this study do not support the use of the space correction KT technique to treat patients with latent or active myofascial trigger points in the upper trapezius muscle.
Diagnosing brain tumours by routine blood tests using machine learning
Authors: Podnar Simon , Kukar Matjaž , Gunčar Gregor , Notar Mateja , Gošnjak Nina , Notar Marko
Published: October 2019

Routine blood test results are assumed to contain much more information than is usually recognised even by the most experienced clinicians. Using routine blood tests from 15,176 neurological patients we built a machine learning predictive model for the diagnosis of brain tumours. We validated the model by retrospective analysis of 68 consecutive brain tumour and 215 control patients presenting to the neurological emergency service. Only patients with head imaging and routine blood test data were included in the validation sample. The sensitivity and specificity of the adapted tumour model in the validation group were 96% and 74%, respectively. Our data demonstrate the feasibility of brain tumour diagnosis from routine blood tests using machine learning. The reported diagnostic accuracy is comparable and possibly complementary to that of imaging studies. The presented machine learning approach opens a completely new avenue in the diagnosis of these grave neurological diseases and demonstrates the utility of valuable information obtained from routine blood tests.
Quantitative and specific detection of cancer-related microRNAs in living cells using surface-enhanced Raman scattering imaging based on hairpin DNA-functionalized gold nanocages
Authors: Wang Zhenyu , Xue Jin , Bi Caili , Xin Heng , Wang Youwei , Cao Xiaowei
Published: October 2019

A highly sensitive surface-enhanced Raman scattering (SERS) strategy based on hairpin DNA-functionalized gold nanocages for the detection of intracellular miR-125a-5p.
Systematic investigation of a quantitative paper-based DNA reader (qPDR) for distance-based quantification of nucleic acids and mercury ions
Authors: Dong Tianyu , Wang Guan A. , Li Michael W. , Li Feng
Published: October 2019

Microfluidic paper-based analytical devices offer exciting opportunities for inexpensive, portable detection of nucleic acids and heavy metal ions in resource-limited settings.
An elemental S/P photocatalyst for hydrogen evolution from water under visible to near-infrared light irradiation
Authors: Cao Qiuyan , Guo Minna , Cao Jing , Lin Haili , Chen Yong , Chen Shifu
Published: October 2019

An elemental S/P photocatalyst exhibits enhanced photocatalytic activity for hydrogen evolution from water due to the co-catalyst effect of S.
Photochemical hydrogen evolution from water by a 1D-network of octahedral Ni6L8 cages
Authors: Kumar Kilaparthi Sravan , Mane Vishwanath S. , Yadav Ashok , Kumbhar Avinash S. , Boomishankar Ramamoorthy
Published: October 2019

An efficient photochemical hydrogen evolution reaction in water supported by a 1D-coordination network of octahedral cages is demonstrated with high turnover numbers.
A dynamic 3D DNA nanostructure based on silicon-supported lipid bilayers: a highly efficient DNA nanomachine for rapid and sensitive sensing
Authors: Wen Zhi-Bin , Peng Xin , Yang Ze-Zhou , Zhuo Ying , Chai Ya-Qin , Liang Wen-Bin , Yuan Ruo
Published: October 2019

Herein, we have developed a dynamic three-dimensional (3D) self-powered DNA nanomachine by anchoring cholesterol-labelled DNA probes to silicon-supported lipid bilayers via cholesterol–lipid interaction.
Mesoporous silica nanobeans dual-functionalized with AIEgens and leaning pillar[6]arene-based supramolecular switches for imaging and stimuli-responsive drug release
Authors: Li Xiangshuai , Han Junyou , Qin Jianchun , Sun Ming , Wu Jiarui , Lei Liancheng , Li Jing , Fang Lei , Yang Ying-Wei
Published: October 2019

Dual-functionalized mesoporous silica nanobeans capable of GSH-dependent turn-on fluorescence and stimuli-responsive drug release are prepared for tumor inhibition and imaging.
Four consecutive reactions in one pot: cascade formation of an unprecedented triphosphatricyclo[3.2.1.02,7]oct-3-ene
Authors: Giese Steven , Buzsáki Dániel , Nyulászi László , Müller Christian
Published: October 2019

Di-pyrone 2H,2′H-[3,3′-bipyran]-2,2′-dione undergoes four consecutive pericyclic reactions with (CH3)3Si-CP to form an unprecedented chiral cage compound triphosphatricyclo[3.2.1.02,7]oct-3-ene in high yield.
Effects of phosphorus dopingviaMn3P2on diamond growth along the (100) surfaces
Authors: Yu Kunpeng , Li Shangsheng , Yang Qun , Leng Kunqiu , Hu Meihua , Su Taichao , Guo Mingming , Gao Guangjin , Wang Junzuo , You Yue
Published: October 2019

In this study, n-type diamond crystals were synthesizedviathe temperature gradient method at 5.6 GPa and 1230–1245 °C by adding a Mn3P2dopant and FeNi catalyst.
Uncertainty estimates for magnetic relaxation times and magnetic relaxation parameters
Authors: Reta Daniel , Chilton Nicholas F.
Published: October 2019

Uncertainties in magnetic relaxation times from AC magnetometry are derived and a program for obtaining them is described, allowing statistically meaningful magnetic relaxation parameterisation.
A Bayesian approach to NMR crystal structure determination
Authors: Engel Edgar A. , Anelli Andrea , Hofstetter Albert , Paruzzo Federico , Emsley Lyndon , Ceriotti Michele
Published: October 2019

We introduce a Bayesian framework for quantifying the reliability of structure determinations for powdered samples on the basis of NMR experiments and chemical shift predictions (with uncertainties) for a pool of candidate structures.
Falloff curves and mechanism of thermal decomposition of CF3I in shock waves
Authors: Cobos C. J. , Sölter L. , Tellbach E. , Troe J.
Published: October 2019

The falloff curves of the unimolecular dissociation CF3I (+Ar) → CF3 + I (+Ar) are modelled by combining quantum-chemical characterization of the potential for the reaction, unimolecular rate theory, and experimental information on collisional energy transfer.
Trends of the macroscopic behaviors of energetic compounds: insights from first-principles calculations
Authors: Sun Chuli , Zhang Weijing , Lü Yongjun , Wang Feng , Guo Wei , Zhang Tonglai , Yao Yugui
Published: October 2019

Studies on the relationship between the microscopic properties and macroscopic behaviors of energetic compounds may provide clues for the synthesis and assessment of novel high energy density materials.
Deoxydehydration of polyols catalyzed by a molybdenum dioxo-complex supported by a dianionic ONO pincer ligand
Authors: Tran Randy , Kilyanek Stefan M.
Published: October 2019

Molybdenum cis-dioxo bis-phenolate ONO complexes were synthesized and have been shown to be active for DODH. Catalysts were screened for activity at 190 °C and ambient pressure, and appreciable alkene yields of up to 59% were obtained.
Proposition of electronic waste as a reference material – part 2: homogeneity, stability, characterization, and uncertainties
Authors: Andrade Daniel Fernandes , Machado Raquel Cardoso , Pereira-Filho Edenir Rodrigues
Published: October 2019

In many cases involving the management of technological materials, such as electronic waste, characterization is performed to determine the correct elemental composition, as well as to detect harmful elements and substances.
Real-time impedimetric droplet measurement (iDM)
Authors: Saateh Abtin , Kalantarifard Ali , Celik Oguz Tolga , Asghari Mohammad , Serhatlioglu Murat , Elbuken Caglar
Published: October 2019

An impedimetric droplet detection tool for real-time analysis of droplet properties.
CD4+versusCD8+ T-lymphocyte identification in an integrated microfluidic chip using light scattering and machine learning
Authors: Rossi Domenico , Dannhauser David , Telesco Mariarosaria , Netti Paolo A. , Causa Filippo
Published: October 2019

Human CD4+ and CD8+ cells are label-free investigated in a compact-dimension microfluidic chip for detailing biophysical properties. A machine learning approach on obtained results allows an accuracy of cell counting and classification up to 88%.