bluuebunny/crossref_metadata_2025 huggingface dataset:
A urinary microRNA panel that is an early predictive biomarker of delayed graft function following kidney transplantation
Authors: Khalid Usman , Newbury Lucy J. , Simpson Kate , Jenkins Robert H. , Bowen Timothy , Bates Lucy , Sheerin Neil S. , Chavez Rafael , Fraser Donald J.
Published: March 2019

Predicting immediate and subsequent graft function is important in clinical decision-making around kidney transplantation, but is difficult using available approaches. Here we have evaluated urinary microRNAs as biomarkers in this context. Profiling of 377 microRNAs in the first urine passed post-transplantation identified 6 microRNAs, confirmed to be upregulated by RT-qPCR in an expanded cohort (miR-9, -10a, -21, -29a, -221, and -429, n = 33, P < 0.05 for each). Receiver operating characteristic analysis showed Area Under the Curve 0.94 for this panel. To establish whether this early signal was sustained, miR-21 was measured daily for 5 days post-transplant, and was consistently elevated in those developing Delayed Graft Function (n = 165 samples from 33 patients, p < 0.05). The biomarker panel was then evaluated in an independent cohort, sampled at varying times in the first week post-transplantation in a separate transplant center. When considered individually, all miRs in the panel showed a trend to increase or a significant increase in those developing delayed Graft Function (miR-9: P = 0.068, mIR-10a: P = 0.397, miR-21: P = 0.003, miR-29a: P = 0.019, miR-221: P = 0.1, and miR-429: P = 0.013, n = 47) with Area Under the Curve 0.75 for the panel. In conclusion, combined measurement of six microRNAs had predictive value for delayed graft function following kidney transplantation.
Wound healing in post-smolt Atlantic salmon (Salmo salar L.)
Authors: Sveen Lene Rydal , Timmerhaus Gerrit , Krasnov Aleksei , Takle Harald , Handeland Sigurd , Ytteborg Elisabeth
Published: March 2019

Skin biopsies (5 mm) taken from behind the dorsal fin on Atlantic salmon post-smolts were followed over a 2 month period. The healing process was dominated by hemostasis, acute inflammation, and epidermal repair the first 14 days post wounding (dpw), as shown through imaging, histological evaluation, and transcriptomics. Most of the immune genes showed decreased expression after two weeks, approaching the levels of intact skin, as also reflected in sections where reduced inflammation in the wound bed was observed. Transcriptional events suggest recruitment of lymphocytes to the wound site during the acute phase, with activation of humoral responses from 14 dpw and onward. From the histology, a more adherent mucus was observed that correlated with altered transcription of glycosyltransferases. This may indicate different properties and functions of the mucus during the wound healing process. Wound contraction started between 14 and 36 dpw. The occurrence of these events was concurrent with granulation tissue formation, melanocyte migration and up-regulation of genes involved in extracellular matrix formation. The presented description of the wound healing processes in Atlantic salmon gives insight into comparative ulcerative biology in mammals and fish and provides both novel and updated knowledge that can be applied for improved best operational practices for fish welfare in aquaculture.
Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study
Authors: Raibman Spector Shir , Mayan Haim , Loebstein Ronen , Markovits Noa , Priel Eldar , Massalha Eias , Shafir Yuval , Gueta Itai
Published: March 2019

5-oxoprolinemia (pyroglutamic acid, PGA) in the absence of acetaminophen use has been rarely reported as a cause for high anion gap metabolic acidosis. We investigated the prevalence and risk factors for elevated PGA concentrations among hospitalized patients with high anion gap metabolic acidosis: We prospectively enrolled patients with high anion gap metabolic acidosis hospitalized in the department of medicine. For each patient we collected the main diagnosis, concurrent medications and laboratory parameters. Spot urine samples were tested for PGA concentration. Levels ≥63 µmol/mmol creatinine were considered elevated. Overall, forty patients were prospectively followed. Mean age was 66.9 (17.9) years. Four (6.3%) patients had a high urine PGA level and demonstrated also lower blood pH (7.2 vs 7.3, p = 0.05) and lower serum lactate concentration (17.5 mg/dl vs 23.0 mg/dl, p = 0.04). Additionally, the high PGA level group consisted of more patients with septic shock [2/4 (50%) vs 3/36 (8.3%)] with a trend towards significance (p = 0.07). In conclusion, PGA might have a role in patients with septic shock and acidosis. Being a treatable condition, PGA should be taken into consideration particularly when no other cause for high anion gap is identified.
Interface effects in hybrid hBN-graphene nanoribbons
Authors: Leon Carlos , Costa Marcio , Chico Leonor , Latgé Andrea
Published: March 2019

We analyze the electronic properties of a hybrid graphene-BN nanoribbon system, using a Hubbard model Hamiltonian within a mean field approximation. Due to the different electronegativities of the boron and nitrogen atoms, an electric field is induced across the zigzag graphene strip, breaking the spin degeneracy of the electronic band structure. Optimal tight-binding parameters are found from first-principles calculations. Edge potentials are proposed as corrections for the on-site energies, modeling the BN-graphene nanoribbon interfaces. We show that half-metallic responses in the hybrid systems may be driven with the help of an external electric field. We also study the role of defects across the graphene nanoribbon and at the h-BN/graphene interface regions. Modulations on the spin-dependent gaps may be achieved depending on the nature and position of the defect, constituting a way towards spin-gap engineering by means of spatial doping.
Ancestral mitochondrial N lineage from the Neolithic ‘green’ Sahara
Authors: Vai Stefania , Sarno Stefania , Lari Martina , Luiselli Donata , Manzi Giorgio , Gallinaro Marina , Mataich Safaa , Hübner Alexander , Modi Alessandra , Pilli Elena , Tafuri Mary Anne , Caramelli David , di Lernia Savino
Published: March 2019

Because Africa’s climate hampers DNA preservation, knowledge of its genetic variability is mainly restricted to modern samples, even though population genetics dynamics and back-migrations from Eurasia may have modified haplotype frequencies, masking ancient genetic scenarios. Thanks to improved methodologies, ancient genetic data for the African continent are now increasingly available, starting to fill in the gap. Here we present newly obtained mitochondrial genomes from two ~7000-year-old individuals from Takarkori rockshelter, Libya, representing the earliest and first genetic data for the Sahara region. These individuals carry a novel mutation motif linked to the haplogroup N root. Our result demonstrates the presence of an ancestral lineage of the N haplogroup in the Holocene “Green Sahara”, associated to a Middle Pastoral (Neolithic) context.
Thresholds for identifying pathological intracranial pressure in paediatric traumatic brain injury
Authors: Kayhanian Saeed , Young Adam M. H. , Ewen Ross L. , Piper Rory J. , Guilfoyle Mathew R. , Donnelly Joseph , Fernandes Helen M. , Garnett Matthew , Smielewski Peter , Czosnyka Marek , Agrawal Shruti , Hutchinson Peter J.
Published: March 2019

Intracranial pressure (ICP) monitoring forms an integral part of the management of severe traumatic brain injury (TBI) in children. The prediction of elevated ICP from imaging is important when deciding on whether to implement invasive ICP monitoring for a patient. However, the radiological markers of pathologically elevated ICP have not been specifically validated in paediatric studies. Here in, we describe an objective, non-invasive, quantitative method of stratifying which patients are likely to require invasive monitoring. A retrospective review of patients admitted to Cambridge University Hospital’s Paediatric Intensive Care Unit between January 2009 and December 2016 with a TBI requiring invasive neurosurgical monitoring was performed. Radiological biomarkers of TBI (basal cistern volume, ventricular volume, volume of extra-axial haematomas) from CT scans were measured and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging. 38 patients were identified. Basal cistern volume was found to correlate significantly with opening ICP (r = −0.53, p < 0.001). The optimal threshold of basal cistern volume for predicting high ICP ($$\ge $$

≥

20 mmHg) was a relative volume of 0.0055 (sensitivity 79%, specificity 80%). Ventricular volume and extra-axial haematoma volume did not correlate significantly with opening ICP. Our results show that the features of pathologically elevated ICP in children may differ considerably from those validated in adults. The development of quantitative parameters can help to predict which patients would most benefit from invasive neurosurgical monitoring and we present a novel radiological threshold for this.
Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells
Authors: Gao Longfei , Huang Shichao , Zhang Hong , Hua Wei , Xin Shunmei , Cheng Lin , Guan Wuqiang , Yu Yongchun , Mao Ying , Pei Gang
Published: March 2019

Glioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient derived xenograft than Temo alone. Our study provided preclinical evidence that the neuronal reprogramming drug cocktail might be a promising strategy to improve the existing treatment for GBM.
Widely targeted metabolome and transcriptome landscapes of Allium fistulosum–A. cepa chromosome addition lines revealed a flavonoid hot spot on chromosome 5A
Authors: Abdelrahman Mostafa , Hirata Sho , Sawada Yuji , Hirai Masami Yokota , Sato Shusei , Hirakawa Hideki , Mine Yoko , Tanaka Keisuke , Shigyo Masayoshi
Published: March 2019

Here, we report a comprehensive analysis of the widely targeted metabolome and transcriptome profiles of Allium fistulosum L. (FF) with the single extra chromosome of shallot [A. cepa L. Aggregatum group (AA)] to clarify the novel gene functions in flavonoid biosynthesis. An exhaustive metabolome analysis was performed using the selected reaction monitoring mode of liquid chromatography–tandem quadrupole mass spectrometry, revealing a specific accumulation of quercetin, anthocyanin and flavone glucosides in AA and FF5A. The addition of chromosome 5A from the shallot to A. fistulosum induced flavonoid accumulation in the recipient species, which was associated with the upregulation of several genes including the dihydroflavonol 4-reductase, chalcone synthase, flavanone 3-hydroxylase, UDP-glucose flavonoid-3-O-glucosyltransferase, anthocyanin 5-aromatic acyltransferase-like, pleiotropic drug resistance-like ATP binding cassette transporter, and MYB14 transcriptional factor. Additionally, an open access Allium Transcript Database (Allium TDB, http://alliumtdb.kazusa.or.jp) was generated by using RNA-Seq data from different genetic stocks including the A. fistulosum–A. cepa monosomic addition lines. The functional genomic approach presented here provides an innovative means of targeting the gene responsible for flavonoid biosynthesis in A. cepa. The understanding of flavonoid compounds and biosynthesis-related genes would facilitate the development of noble Allium varieties with unique chemical constituents and, subsequently, improved plant stress tolerance and human health benefits.
Optimal cardiac strategy based on the history of myocardial infarction in type 2 diabetic patients with coronary artery disease
Authors: Tsujimoto Tetsuro , Kajio Hiroshi
Published: March 2019

The aim of this study was to evaluate the association between the cardiac treatment strategy and cardiac event risk in type 2 diabetic patients with coronary artery disease (CAD) based on the history of myocardial infarction. Using Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data, a Cox proportional hazard model was used for calculating hazard ratios (HRs) for major cardiac events in patients receiving early revascularization or intensive medical therapy. Patients without (n = 1,557) and with myocardial infarction (n = 736) were separately analyzed. In patients without myocardial infarction, risk of major cardiac events was similar for percutaneous coronary intervention and intensive medical therapy groups, whereas it was significantly lower in the coronary artery bypass grafting group than in the intensive medical therapy group (HR: 0.48, 95% confidence interval [95%CI]: 0.30–0.76, P = 0.002). Conversely, in patients with myocardial infarction, risk of major cardiac events was significantly higher in the early revascularization group than in the intensive medical therapy group (HR: 1.47, 95%CI: 1.03–2.11, P = 0.03). In type 2 diabetic patients with CAD, benefits of early revascularization were observed only in those without previous myocardial infarction. For patients with previous myocardial infarction, intensive medical therapy exerted superior benefits.
Combined oral contraceptive pill-exposure alone does not reduce the risk of bacterial vaginosis recurrence in a pilot randomised controlled trial
Authors: Vodstrcil Lenka A. , Plummer Ms Erica , Fairley Christopher K. , Tachedjian Gilda , Law Matthew G. , Hocking Jane S. , Worthington Ms Karen , Grant Ms Mieken , Okoko Nita , Bradshaw Catriona S.
Published: March 2019

We conducted a pilot open-label randomised controlled trial of combined (oestrogen-progesterone) oral contraceptive pill (COCP)-exposure aimed to examine its effect on BV-recurrence following first-line antibiotics compared to antibiotics alone. Ninety-five women with symptomatic BV were prescribed antibiotic therapy, randomised to COCP-exposure (intervention) or current non-hormonal contraceptive practices (control) and followed monthly for six-months or until BV-recurrence. Modified intention-to-treat methods requiring either ≥1 clinical (primary/Amsel-outcome) or ≥1 microbiological (secondary/Nugent-outcome) BV-recurrence assessment were applied to determine cumulative recurrence rates. Secondary Cox regression analyses assessed factors associated with recurrence in all women. 92/95 women randomised provided baseline requirements. BV-recurrence rates were similar in women randomised to the COCP (primary/Amsel-outcome: 10/100PY, 95%CI: 6,19/100PY) compared to controls (14/100PY, 95%CI: 9, 21/100PY, p = 0.471). In secondary analyses sex with the same pre-treatment regular sexual partner (RSP; Amsel: Adjusted Hazard Ratio [AHR] = 3.13, 95%CI: 1.41, 6.94, p = 0.005; Nugent: AHR = 2.97, 95%CI: 1.49, 5.83, p = 0.002) and BV-history (Amsel: AHR = 3.03, 95%CI: 1.14, 6.28; Nugent: AHR = 2.78, 95%CI: 1.22, 6.33) were associated with increased BV-recurrence. This pilot RCT of COCP-exposure did not improve BV cure but found sex with an RSP and BV-history were associated with recurrence, although impacted by sample size and attrition. These data indicate reinfection from an untreated RSP and persistence of BV-associated bacteria are integral to the pathogenesis of recurrence and may overwhelm potential beneficial effects of hormonal contraception on the vaginal microbiota.
Inter-relationship between subtropical Pacific sea surface temperature, Arctic sea ice concentration, and North Atlantic Oscillation in recent summers
Authors: Lim Young-Kwon , Cullather Richard I. , Nowicki Sophie M. J. , Kim Kyu-Myong
Published: March 2019

The inter-relationship between subtropical western–central Pacific sea surface temperatures (STWCPSST), sea ice concentrations in the Beaufort Sea (SICBS), and the North Atlantic Oscillation (NAO) in summer are investigated over the period 1980–2016. It is shown that the Arctic response to the remote impact of the Pacific SST is more dominant in recent summers, leading to a frequent occurrence of the negative phase of the NAO following the STWCPSST increase. Lag–correlations of STWCPSST positive (negative) anomalies in spring with the negative (positive) NAO and SICBS loss (recovery) in summer have increased over the last two decades, reaching r = 0.4–0.5 with significance at the 5 percent level. Both observations and the atmospheric general circulation model experiments suggest that the positive STWCPSST anomaly and subsequent planetary-scale wave propagation act to increase the Arctic upper-level geopotential heights and temperatures in the following season. This response extends to Greenland, providing favorable conditions for developing the negative phase of the NAO. Connected with this atmospheric response, SIC and surface albedo decrease with an increase in the surface net shortwave flux over the Beaufort Sea. Examination of the surface energy balance (radiative and turbulent fluxes) reveals that surplus energy that can heat the surface increases over the Arctic, enhancing the SIC reduction.
Shared and unique genomic structural variants of different histological components within testicular germ cell tumours identified with mate pair sequencing
Authors: Bryce Alan H. , Egan Jan B. , Smadbeck James B. , Johnson Sarah H. , Murphy Stephen J. , Harris Faye R. , Halling Geoffrey C. , Terra Simone B. S. P. , Cheville John , Pagliaro Lance , Leibovich Brad , Costello Brian A. , Vasmatzis George
Published: March 2019

Post-pubertal testicular germ-cell tumours (TGCTs) can present with a variety of distinct histologies which are nevertheless lineage related and often co-occurring. The exact lineage relationships and developmental pathways leading to the different histologies is debated. In order to investigate the relationship of histologic populations, mate-pair sequencing (MPseq) and exome sequencing (ExomeSeq) were conducted on different histological populations within the same tumour. Ten TGCTs with 1–3 histologic types/tumour were sequenced. Junctions of somatic chromosomal rearrangements were identified on a per genome basis, with germ cell neoplasia in situ possessing the least (median 1, range 0–4) and embryonal carcinoma the most (median 8.5, range 6–12). Copy number variation revealed gains and losses, including isoform 12p (i12p) (10/10 samples), and chromosomes 7, 8, and 21 gains (7/10 samples). Mapping of shared junctions within a tumour revealed lineage relationships, but only i12p was shared between patients. ExomeSeq from two cases demonstrated a high level of copy-neutral loss of heterozygosity. Parallel assessment of separate histologies within a single TGCT demonstrated cumulative and divergent changes, suggesting the importance of parallel sequencing for detection of relevant biomarkers.
Unusual properties and potential applications of strain BN-MS2 (M = Mo, W) heterostructures
Authors: Su Jie , He Jian , Zhang Junjing , Lin Zhenhua , Chang Jingjing , Zhang Jincheng , Hao Yue
Published: March 2019

Heterostructures receive intensive attentions due to their excellent intrinsic properties and wide applications. Here, we investigate the natural physical properties and performances of strain BN-MS2 (M = Mo, W) heterostructure by density functional theory. Different to compressive monolayer MS2, corresponding BN-MS2 heterostructures keep direct band-gap characters because effects of charge transfer on anti-bonding dz2 orbitals are stronger than those of Poisson effect. Mexican-hat-like bands without magnetic moments are observed at strain BN-MS2 heterostructures when the compression is enough. Consequently, electron mobilities of strain BN-MS2 heterostructures are slightly reduced at first and then enlarged with increasing compressive strain. Note that, strain BN-MS2 heterostructures reduce the band edges of MS2 layers and extend their application in photocatalytic water splitting. But just the n-type and p-type Schottky barriers of devices with strain BN-MS2 heterostructures are reduced and even vanished with the increasing tensile and compressive, respectively. Besides, electron mobilities of strain BN-MoS2 and BN-WS2 heterostructures can be enhanced to 1290 and 1926 cm2  V −1 s−1, respectively, with increasing tensile strain. Interestingly, the exciton binding energies of strain BN-MS2 heterostructures exhibit oscillation variations, different to those of strain monolayer MS2.
Vacancy cluster in ZnO films grown by pulsed laser deposition
Authors: Wang Zilan , Luo Caiqin , Anwand W. , Wagner A. , Butterling M. , Rahman M. Azizar , Phillips Matthew R. , Ton-That Cuong , Younas M. , Su Shichen , Ling Francis Chi-Chung
Published: March 2019

Undoped and Ga-doped ZnO films were grown on c-sapphire using pulsed laser deposition (PLD) at the substrate temperature of 600 °C. Positron annihilation spectroscopy study (PAS) shows that the dominant VZn-related defect in the as-grown undoped ZnO grown with relative low oxygen pressure P(O2) is a vacancy cluster (most likely a VZn-nVO complex with n = 2, 3) rather than the isolated VZn which has a lower formation energy. Annealing these samples at 900 °C induces out-diffusion of Zn from the ZnO film into the sapphire creating the VZn at the film/sapphire interface, which favors the formation of vacancy cluster containing relatively more VZn. Increasing the P(O2) during growth also lead to the formation of the vacancy cluster with relatively more VZn. For Ga-doped ZnO films, the oxygen pressure during growth has significant influence on the electron concentration and the microstructure of the VZn-related defect. Green luminescence (GL) and yellow luminescence (YL) were identified in the cathodoluminescence study (CL) study, and both emission bands were quenched after hydrogen plasma treatment. The origin of the GL is discussed.
Geometric frustration in ordered lattices of plasmonic nanoelements
Authors: Conde-Rubio Ana , Fraile Rodríguez Arantxa , Espinha André , Mihi Agustín , Pérez-Murano Francesc , Batlle Xavier , Labarta Amílcar
Published: March 2019

Inspired by geometrically frustrated magnetic systems, we present the optical response of three cases of hexagonal lattices of plasmonic nanoelements. All of them were designed using a metal-insulator-metal configuration to enhance absorption of light, with elements in close proximity to exploit near-field coupling, and with triangular symmetry to induce frustration of the dipolar polarization in the gaps between neighboring structures. Both simulations and experimental results demonstrate that these systems behave as perfect absorbers in the visible and/or the near infrared. Besides, the numerical study of the time evolution shows that they exhibit a relatively extended time response over which the system fluctuates between localized and collective modes. It is of particular interest the echoed excitation of surface lattice resonance modes, which are still present at long times because of the geometric frustration inherent to the triangular lattice. It is worth noting that the excitation of collective modes is also enhanced in other types of arrays where dipolar excitations of the nanoelements are hampered by the symmetry of the array. However, we would like to emphasize that the enhancement in triangular arrays can be significantly larger because of the inherent geometric incompatibility of dipolar excitations and three-fold symmetry axes.
Effect of strain relaxation on performance of InGaN/GaN green LEDs grown on 4-inch sapphire substrate with sputtered AlN nucleation layer
Authors: Hu Hongpo , Zhou Shengjun , Wan Hui , Liu Xingtong , Li Ning , Xu Haohao
Published: March 2019

Here we demonstrate high-brightness InGaN/GaN green light emitting diodes (LEDs) with in-situ low-temperature GaN (LT-GaN) nucleation layer (NL) and ex-situ sputtered AlN NL on 4-inch patterned sapphire substrate. Compared to green LEDs on LT-GaN (19 nm)/sapphire template, green LEDs on sputtered AlN (19 nm)/template has better crystal quality while larger in-plane compressive strain. As a result, the external quantum efficiency (EQE) of green LEDs on sputtered AlN (19 nm)/sapphire template is lower than that of green LEDs on LT-GaN (19 nm)/sapphire template due to strain-induced quantum-confined Stark effect (QCSE). We show that the in-plane compressive strain of green LEDs on sputtered AlN/sapphire templates can be manipulated by changing thickness of the sputtered AlN NL. As the thickness of sputtered AlN NL changes from 19 nm to 40 nm, the green LED on sputtered AlN (33 nm)/sapphire template exhibits the lowest in-plane compressive stress and the highest EQE. At 20 A/cm2, the EQE of 526 nm green LEDs on sputtered AlN (33 nm)/sapphire template is 36.4%, about 6.1% larger than that of the green LED on LT-GaN (19 nm)/sapphire template. Our experimental data suggest that high-efficiency green LEDs can be realized by growing InGaN/GaN multiple quantum wells (MQWs) on sputtered AlN/sapphire template with reduced in-plane compressive strain and improved crystal quality.
Modelling and fitting the Polaron Pair Magnetoconductance model to obtain a realistic local hyperfine field in Tris-(8-hydroxyquinoline)aluminium based diodes
Authors: Weng Zhichao , Gillin William P. , Kreouzis Theo
Published: March 2019

The Polaron Pair (PP) model has been successfully applied to magnetoconductance (MC) in organic semiconductor devices under ultra-small magnetic fields (USMFE). We report µT resolution MC measurements carried out with high sensitivity (better than 10−6) on the common organic semiconductor tris-(8-hydroxyquinoline)aluminium in the range ±500 µT displaying clear minima at ~±240 µT. Unlike traditional approaches, where device MC is simply evaluated using the PP model using nominal parameters for microscopic quantities such as the local hyperfine magnetic field, we have carried out actual fitting of the PP MC model to the experimentally obtained data. The fitting procedure yields physically realistic values for the polaron pair decay rate, local hyperfine magnetic field and triplet contribution to dissociation namely: $$k$$
k
 = 28.6 ± 9.7 MHz, $${B}_{hf}$$

B

h
f

 = 0.34 ± 0.04 mT and $${\delta }_{TS}$$

δ

T
S

 = 0.99 ± 0.01 respectively. The local hyperfine field obtained by fitting is in excellent agreement with independently calculated values for this system and is reproducible across different devices and independent of drive conditions. This demonstrates the applicability of the fitting approach to any organic USMFE MC data for obtaining microscopic parameter values.
Phase transitions and asymmetry between signal comprehension and production in biological communication
Authors: Salahshour Mohammad , Rouhani Shahin , Roudi Yasser
Published: March 2019

We introduce a model for collective information acquisition from the environment, in a biological population. In this model, individuals can make noisy observations of the environment, and communicate their observation by production and comprehension of signals. As the communication noise decreases, the model shows an order-disorder transition from a disordered phase in which no consensus about the environmental state exists to an ordered phase where the population forms a consensus about the environmental state. The ordered phase itself is composed of an informed consensus, in which the correct belief about the environment prevails, and an uninformed consensus phase, in which consensus on a random belief about the environmental state is formed. The probability of reaching informed consensus increases with increasing the observation probability. This phenomenology implies that a maximum noise level, and a minimum observation probability are necessary for informed consensus in a communicating population. Furthermore, we show that the fraction of observant individuals needed for the group to reach informed consensus decreases with increasing population size. This results from a shift in the uninformed-informed transition to smaller observation probabilities by increasing population size. Importantly, we also find that an amount of noise in signal production deteriorates the information flow and the inference capability, more than the same amount of noise in comprehension. This finding implies that there is higher selection pressure to reduce noise in production of signals compared to comprehension. Regarding this asymmetry, we propose an experimental design to separately measure comprehension and production noise in a given population and test the predicted asymmetry.
Optogenetic stimulation promotes Schwann cell proliferation, differentiation, and myelination in vitro
Authors: Jung Kyuhwan , Park Ji Hye , Kim Sung-Yon , Jeon Noo Li , Cho Sung-Rae , Hyung Sujin
Published: March 2019

Schwann cells (SCs) constitute a crucial element of the peripheral nervous system, by structurally supporting the formation of myelin and conveying vital trophic factors to the nervous system. However, the functions of SCs in developmental and regenerative stages remain unclear. Here, we investigated how optogenetic stimulation (OS) of SCs regulates their development. In SC monoculture, OS substantially enhanced SC proliferation and the number of BrdU+-S100ß+-SCs over time. In addition, OS also markedly promoted the expression of both Krox20 and myelin basic protein (MBP) in SC culture medium containing dBcAMP/NRG1, which induced differentiation. We found that the effects of OS are dependent on the intracellular Ca2+ level. OS induces elevated intracellular Ca2+ levels through the T-type voltage-gated calcium channel (VGCC) and mobilization of Ca2+ from both inositol 1,4,5-trisphosphate (IP3)-sensitive stores and caffeine/ryanodine-sensitive stores. Furthermore, we confirmed that OS significantly increased expression levels of both Krox20 and MBP in SC-motor neuron (MN) coculture, which was notably prevented by pharmacological intervention with Ca2+. Taken together, our results demonstrate that OS of SCs increases the intracellular Ca2+ level and can regulate proliferation, differentiation, and myelination, suggesting that OS of SCs may offer a new approach to the treatment of neurodegenerative disorders.
Effect of encapsulation on electronic transport properties of nanoscale Cu(111) films
Authors: Shinde Prashant P. , Adiga Shashishekar P. , Pandian Shanthi , Mayya K. Subramanya , Shin Hyeon-Jin , Park Seongjun
Published: March 2019

The stiff compromise between reliability and conductivity of copper interconnects used in sub-nanometer nodes has brought into focus the choice of encapsulation material. While reliability was the primary driver so far, herein, we investigate how electronic conductivity of Cu(111) thin films is influenced by the encapsulation material using density functional theory and Boltzmann transport equation. Atomically thin 2D materials, namely conducting graphene and insulating graphane both retain the conductivity of Cu films whereas partially hydrogenated graphene (HGr) results in reduction of surface density of states and a reduction in Cu film conductivity. Among transition metal elements, we find that atoms in Co encapsulation layer, which essentially act as magnetic impurities, serve as electron scattering centres resulting in a decrease in conductivity by at least 15% for 11 nm thick Cu film. On the other hand, Mo, Ta, and Ru have more favorable effect on conductivity when compared to Co. The cause of decrease in conductivity for Co and HGr is discussed by investigating the electronic band structure and density of states. Our DFT calculations suggest that pristine graphene sheet is a good encapsulation material for advanced Cu interconnects both from chemical protection and conductivity point of view.
Selection of suitable reference genes for gene expression analysis in gills and liver of fish under field pollution conditions
Authors: Rojas-Hernandez Noemí , Véliz David , Vega-Retter Caren
Published: March 2019

To understand the role of gene expression in adaptive variation, it is necessary to examine expression variation in an ecological context. Quantitative real-time PCR (qPCR) is considered the most accurate and reliable technique to measure gene expression and to validate the data obtained by RNA-seq; however, accurate normalization is crucial. In Chile, the freshwater silverside fish Basilichthys microlepidotus inhabits both polluted and nonpolluted areas, showing differential gene expression related to pollution. In this study, we infer the stability of six potential reference genes (tubulin alpha, hypoxanthine-guanine phosphoribosyltransferase, glyceraldehyde-3-phosphate dehydrogenase, beta-actin, 60S ribosomal protein L13, and 60S ribosomal protein L8) in the gills and liver of silverside individuals inhabiting polluted and nonpolluted areas. To validate the reference genes selected, the most and least stable reference genes were used to normalize two target transcripts, one for each organ. The RefFinder tool was used to analyze and identify the most stably expressed genes. The 60S ribosomal protein L8 gene was ranked as the most stable gene for both organs. Our results show that reference gene selection influences the detection of differences in the expression levels of target genes in different organs and, also highlighting candidate reference genes that could be used in field studies.
Dose/Volume histogram patterns in Salivary Gland subvolumes influence xerostomia injury and recovery
Authors: Han Peijin , Lakshminarayanan Pranav , Jiang Wei , Shpitser Ilya , Hui Xuan , Lee Sang Ho , Cheng Zhi , Guo Yue , Taylor Russell H. , Siddiqui Sauleh A. , Bowers Michael , Sheikh Khadija , Kiess Ana , Page Brandi R. , Lee Junghoon , Quon Harry , McNutt Todd R.
Published: March 2019

Xerostomia is a common consequence of radiotherapy in head and neck cancer. The objective was to compare the regional radiation dose distribution in patients that developed xerostomia within 6 months of radiotherapy and those recovered from xerostomia within 18 months post-radiotherapy. We developed a feature generation pipeline to extract dose volume histogram features from geometrically defined ipsilateral/contralateral parotid glands, submandibular glands, and oral cavity surrogates for each patient. Permutation tests with multiple comparisons were performed to assess the dose difference between injury vs. non-injury and recovery vs. non-recovery. Ridge logistic regression models were applied to predict injury and recovery using clinical features along with dose features (D10-D90) of the subvolumes extracted from oral cavity and salivary gland contours + 3 mm peripheral shell. Model performances were assessed by the area under the receiver operating characteristic curve (AUC) using nested cross-validation. We found that different regional dose/volume metrics patterns exist for injury vs. recovery. Compared to injury, recovery has increased importance to the subvolumes receiving lower dose. Within the subvolumes, injury tends to have increased importance towards D10 from D90. This suggests that different threshold for xerostomia injury and recovery. Injury is induced by the subvolumes receiving higher dose, and the ability to recover can be preserved by further reducing the dose to subvolumes receiving lower dose.
Evaluation of detection probabilities at the water-filtering and initial PCR steps in environmental DNA metabarcoding using a multispecies site occupancy model
Authors: Doi Hideyuki , Fukaya Keiichi , Oka Shin-ichiro , Sato Keiichi , Kondoh Michio , Miya Masaki
Published: March 2019

Environmental DNA (eDNA) metabarcoding is a recently developed method to assess biodiversity based on a high-throughput parallel DNA sequencing applied to DNA present in the ecosystem. Although eDNA metabarcoding enables a rapid assessment of biodiversity, it is prone to species detection errors that may occur at sequential steps in field sampling, laboratory experiments, and bioinformatics. In this study, we illustrate how the error rates in the eDNA metabarcoding-based species detection can be accounted for by applying the multispecies occupancy modelling framework. We report a case study with the eDNA sample from an aquarium tank in which the detection probabilities of species in the two major steps of eDNA metabarcoding, filtration and PCR, across a range of PCR annealing temperatures, were examined. We also show that the results can be used to examine the efficiency of species detection under a given experimental design and setting, in terms of the efficiency of species detection, highlighting the usefulness of the multispecies site occupancy modelling framework to study the optimum conditions for molecular experiments.
Randomized Controlled Trial comparing the effectiveness of structured-play (ENGAGE) and behavior management (TRIPLE P) in reducing problem behaviors in preschoolers
Authors: Healey Dione , Healey Matthew
Published: March 2019

Children’s behavior problems are a growing concern in our society; and are associated with a wide array of adverse lifespan outcomes. Current treatments are not without limitations and while effective for many, do not help all children. As such, additional treatment options are required. Sixty families of children aged 3 and 4 years participated. In order to participate, children needed to have a T-score of 60 or above on the parent rated Hyperactivity subscale on the BASC-2. Families were randomly assigned to either a structured play-based intervention (ENGAGE; n = 29), or to the current gold standard treatment for preschool behavior problems, behavior management (Triple P; n = 31). This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR); trial number ACTRN12617001432303; trial web address: http://www.anzctr.org.au/ACTRN12617001432303.aspx; date registered; 10/10/2017. ENGAGE was found to be as effective as Triple P in reducing parent-rated problem behaviors in pre-schoolers (i.e., Hyperactivity, Attention Problems, and Aggression); with gains maintained over a 12-month follow-up period, for both interventions. These findings indicate that structured play is an equally effective alternative way to manage difficult behavior in preschoolers and compliments our current treatment options.
Exploiting heat shock protein expression to develop a non-invasive diagnostic tool for breast cancer
Authors: Crouch Brian T. , Gallagher Jennifer , Wang Roujia , Duer Joy , Hall Allison , Soo Mary Scott , Hughes Philip , Haystead Timothy , Ramanujam Nirmala
Published: March 2019

Leveraging the unique surface expression of heat shock protein 90 (Hsp90) in breast cancer provides an exciting opportunity to develop rapid diagnostic tests at the point-of-care setting. Hsp90 has previously been shown to have elevated expression levels across all breast cancer receptor subtypes. We have developed a non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens and validated our approach in clinical samples from breast cancer patients across estrogen receptor positive, Her2-overexpressing, and triple negative receptor subtypes. Utilizing a pre-clinical biopsy model, we optimized three imaging parameters that may affect the specificity of HS-27 based diagnostics – time between tissue excision and staining, agent incubation time, and agent dose, and translated our strategy to clinical breast cancer samples. Findings indicated that HS-27 florescence was highest in tumor tissue, followed by benign tissue, and finally followed by mammoplasty negative control samples. Interestingly, fluorescence in tumor samples was highest in Her2+ and triple negative subtypes, and inversely correlated with the presence of tumor infiltrating lymphocytes indicating that HS-27 fluorescence increases in aggressive breast cancer phenotypes. Development of a Gaussian support vector machine classifier based on HS-27 fluorescence features resulted in a sensitivity and specificity of 82% and 100% respectively when classifying tumor and benign conditions, setting the stage for rapid and automated tissue diagnosis at the point-of-care.
Water-Deprived Parasitic Wasps (Pachycrepoideus vindemmiae) Kill More Pupae of a Pest (Drosophila suzukii) as a Water-Intake Strategy
Authors: Bezerra Da Silva Cherre Sade , Price Briana Elizabeth , Walton Vaughn M.
Published: March 2019

Most organisms must ingest water to compensate for dehydration. In parasitic wasps, the importance of water and the behaviors driving its consumption are poorly understood. Here, we describe a water-intake strategy of Pachycrepoideus vindemmiae, a parasitoid of spotted-wing drosophila (SWD, Drosophila suzukii). Longevity measurements indicated that P. vindemmiae benefits from drinking water and from host-feeding on the water-rich hemolymph of SWD pupae. After exposing wasps to different water regimens, we observed increased host-feeding in water-deprived wasps despite honey availability. This resulted in greater SWD mortality because the host-feeding process killed the pupae, and because wasps that engaged in greater host-feeding parasitized more hosts. Behavioral observations showed that the host-feeding time of water-deprived wasps doubled compared to water-fed individuals. Host-feeding did not affect parasitoid offspring mortality. We conclude that P. vindemmiae benefits from ingesting water and that it host-feeds on SWD pupae as a water-intake strategy. These are interesting findings not only because water has rarely been reported as a critical nutrient for adult parasitoids, but especially because preying for the purpose of hydration is not a common strategy in nature. This strategy enhances parasitoid survival and reproduction, with positive consequences for its host-killing capacity and potential as a biocontrol agent.
Differential Sensitivity to Plasmodium yoelii Infection in C57BL/6 Mice Impacts Gut-Liver Axis Homeostasis
Authors: Denny Joshua E. , Powers Joshua B. , Castro Hector F. , Zhang Jingwen , Joshi-Barve Swati , Campagna Shawn R. , Schmidt Nathan W.
Published: March 2019

Experimental models of malaria have shown that infection with specific Plasmodium species in certain mouse strains can transiently modulate gut microbiota and cause intestinal shortening, indicating a disruption of gut homeostasis. Importantly, changes in gut homeostasis have not been characterized in the context of mild versus severe malaria. We show that severe Plasmodium infection in mice disrupts homeostasis along the gut-liver axis in multiple ways compared to mild infection. High parasite burden results in a larger influx of immune cells in the lamina propria and mice with high parasitemia display specific metabolomic profiles in the ceca and plasma during infection compared to mice with mild parasitemia. Liver damage was also more pronounced and longer lasting during severe infection, with concomitant changes in bile acids in the gut. Finally, severe Plasmodium infection changes the functional capacity of the microbiota, enhancing bacterial motility and amino acid metabolism in mice with high parasite burden compared to a mild infection. Taken together, Plasmodium infections have diverse effects on host gut homeostasis relative to the severity of infection that may contribute to enteric bacteremia that is associated with malaria.
A dynamically interacting flexible loop assists oligomerisation of the Caenorhabditis elegans centriolar protein SAS-6
Authors: Busch Julia M. C. , Erat Michèle C. , Blank Iris D. , Musgaard Maria , Biggin Philip C. , Vakonakis Ioannis
Published: March 2019

Centrioles are conserved organelles fundamental for the organisation of microtubules in animal cells. Oligomerisation of the spindle assembly abnormal protein 6 (SAS-6) is an essential step in the centriole assembly process and may act as trigger for the formation of these organelles. SAS-6 oligomerisation is driven by two independent interfaces, comprising an extended coiled coil and a dimeric N-terminal globular domain. However, how SAS-6 oligomerisation is controlled remains unclear. Here, we show that in the Caenorhabditis elegans SAS-6, a segment of the N-terminal globular domain, unresolved in crystallographic structures, comprises a flexible loop that assists SAS-6 oligomerisation. Atomistic molecular dynamics simulations and nuclear magnetic resonance experiments suggest that transient interactions of this loop across the N-terminal dimerisation interface stabilise the SAS-6 oligomer. We discuss the possibilities presented by such flexible SAS-6 segments for the control of centriole formation.
Metal-enhanced fluorescence and excited state dynamics of carotenoids in thin polymer films
Authors: Lee Jaebeom , Song Junghyun , Lee Daedu , Pang Yoonsoo
Published: March 2019

Metal-enhanced fluorescence of carotenoids, all-trans-β-carotene and 8′-apo-β-carotene-8′-al dispersed in thin layers of polystyrene and polyethylene glycol were investigated by time-resolved fluorescence spectroscopy. The weak emission signals of carotenoids in polymer films were increased by 4–40 times in the presence of a silver island film and the emission lifetimes of both carotenoids were measured as significantly shortened. The energy transfer from the intermediate states of carotenoids to the silver islands and the subsequent surface plasmon coupled emission were proposed for the mechanisms of metal-enhanced fluorescence. The fluorescence enhancements of carotenoids in the polymer films were also investigated statistically over a wide area of the silver island films.
Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP
Authors: Andersson Tilde , Ertürk Bergdahl Gizem , Saleh Karim , Magnúsdóttir Helga , Stødkilde Kristian , Andersen Christian Brix Folsted , Lundqvist Katarina , Jensen Anders , Brüggemann Holger , Lood Rolf
Published: March 2019

Cutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes’s secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.