bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractive index variation in a free-standing diamond thin film induced by irradiation with fully transmitted high-energy protons
Authors: Lagomarsino S. , Calusi S. , Massi M. , Gelli N. , Sciortino S. , Taccetti F. , Giuntini L. , Sordini A. , Vannoni M. , Bosia F. , Monticone D. Gatto , Olivero P. , Fairchild B. A. , Kashyap P. , Alves A. D. C. , Strack M. A. , Prawer S. , Greentree A. D.
Published: March 2017

Ion irradiation is a widely employed tool to fabricate diamond micro- and nano-structures for applications in integrated photonics and quantum optics. In this context, it is essential to accurately assess the effect of ion-induced damage on the variation of the refractive index of the material, both to control the side effects in the fabrication process and possibly finely tune such variations. Several partially contradictory accounts have been provided on the effect of the ion irradiation on the refractive index of single crystal diamond. These discrepancies may be attributable to the fact that in all cases the ions are implanted in the bulk of the material, thus inducing a series of concurrent effects (volume expansion, stress, doping, etc.). Here we report the systematic characterization of the refractive index variations occurring in a 38 µm thin artificial diamond sample upon irradiation with high-energy (3 MeV and 5 MeV) protons. In this configuration the ions are fully transmitted through the sample, while inducing an almost uniform damage profile with depth. Therefore, our findings conclusively identify and accurately quantify the change in the material polarizability as a function of ion beam damage as the primary cause for the modification of its refractive index.
High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy
Authors: Kivelä A. M. , Huusko J. , Gurzeler E. , Laine A. , Dijkstra M. H. , Dragneva G. , Andersen C. B. F. , Moestrup S. K. , Ylä-Herttuala S.
Published: March 2017

Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE−/− mice have much higher plasma transgene levels compared to LDLR-deficient mice. We also found that specific lipoprotein receptors play an important role in adenoviral transduction. These findings suggest that high plasma lipid levels, especially apoE-containing lipoproteins, reduce efficacy of adenoviral transduction in mice, which implies that high cholesterol levels in humans could be protective against viral infections and also lead to insufficient transgene expression in clinical trials using adenoviral vectors.
Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury
Authors: Zhang Haosu , Dai Rui , Qin Pengmin , Tang Weijun , Hu Jin , Weng Xuchu , Wu Xing , Mao Ying , Wu Xuehai , Northoff Georg
Published: March 2017

Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.
The feature-specific propagation of orientation and direction adaptation from areas 17 to 21a in cats
Authors: Li Zhong , Meng Jianjun , Li Hongjian , Jin Anqi , Tang Qijun , Zhu Jianbin , Yu Hongbo
Published: March 2017

Adaptation plays a key role in visual information processing, and investigations on the adaptation across different visual regions will be helpful to understand how information is processed dynamically along the visual streams. Recent studies have found the enhanced adaptation effects in the early visual system (from LGN to V1) and the dorsal stream (from V1 to MT). However, it remains unclear how adaptation effect propagates along the form/orientation stream in the visual system. In this study, we compared the orientation and direction adaptation evoked by drifting gratings and stationary flashing gratings, as well as moving random dots, in areas 17 and 21a simultaneously of cats. Recorded by single-unit and intrinsic signal optical imaging, induced by both top-up and biased adaptation protocols, the orientation adaptation effect was greater in response decline and preferred orientation shifts in area 21a compared to area 17. However, for the direction adaptation, no difference was observed between these two areas. These results suggest the feature-specific propagation of the adaptation effect along the visual stream.
Autoassociative Memory and Pattern Recognition in Micromechanical Oscillator Network
Authors: Kumar Ankit , Mohanty Pritiraj
Published: March 2017

Towards practical realization of brain-inspired computing in a scalable physical system, we investigate a network of coupled micromechanical oscillators. We numerically simulate this array of all-to-all coupled nonlinear oscillators in the presence of stochasticity and demonstrate its ability to synchronize and store information in the relative phase differences at synchronization. Sensitivity of behavior to coupling strength, frequency distribution, nonlinearity strength, and noise amplitude is investigated. Our results demonstrate that neurocomputing in a physically realistic network of micromechanical oscillators with silicon-based fabrication process can be robust against noise sources and fabrication process variations. This opens up tantalizing prospects for hardware realization of a low-power brain-inspired computing architecture that captures complexity on a scalable manufacturing platform.
MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
Authors: Sun Yuxin , Xu Jia , Xu Liangliang , Zhang Jinfang , Chan Kaiming , Pan Xiaohua , Li Gang
Published: March 2017

Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most significantly up-regulated miRNAs in DO. The further investigation also showed that miR-503 was upregulated during osteogenesis in mesenchymal stem cells of rats, and overexpression of miR-503 significantly promoted osteogenesis in vitro and accelerated mineralization in DO process in vivo. By using bioinformatic investigations and luciferase activities, we successfully demonstrated that Smurf1, a negative regulator of osteogenesis, was a real target of miR-503. Furthermore, Smurf1 knockdown promoted osteogenesis and antagomir-503 abolished the promotive effect, suggesting that miR-503 mediated osteogenic differentiation via suppressing Smurf1 expression. To sum up, these findings indicated that miR-503 promoted osteogenesis and accelerated bone formation, which may shed light on the development for a potential therapeutic target for bone repair.
Risk factors of post-operative severe hyperlactatemia and lactic acidosis following laparoscopic resection for pheochromocytoma
Authors: Wu Shubin , Chen Weiyun , Shen Le , Xu Li , Zhu Afang , Huang Yuguang
Published: March 2017

Severe hyperlactatemia (SH)/lactic acidosis (LA) after laparoscopic resection of pheochromocytoma is an infrequently reported complication. The study aims to investigate the incidence of this complication and to determine the clinical risk factors. Patients who underwent laparoscopic resection for pheochromocytoma between 2011 and 2014 at Peking Union Medical College Hospital were enrolled. LA was defined as pH < 7.35, bicarbonate <20 mmol/L, and serum lactate ≥5 mmol/L; SH as lactate ≥5 mmol/L; and moderate hyperlactatemia (MH) as lactate 2.5–5.0 mmol/L without evidence of acidosis (pH > 7.35 and/or bicarbonate >20 mmol/L). Data concerning patient demographics, clinical history, and laboratory results were collected and statistical analyses were performed. Out of 145 patients, 59 (40.7%) developed post-operative hyperlactatemia. The incidences of MH and SH/LA were 25.5% and 15.2%, respectively. Multivariate analysis demonstrated that body mass index (BMI) (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.016–1.426), 24-hour urine epinephrine concentration (OR, 1.012; 95% CI, 1.002–1.022), and tumor size (OR, 1.571; 95% CI, 1.102–2.240) were independent predictors of post-operative SH/LA. The data show that post-operative SH/LA is not a rare complication after pheochromocytoma resection and may be closely associated with higher BMI, larger tumor size, and higher levels of urine epinephrine.
Investigation and manipulation of metabolically active methanogen community composition during rumen development in black goats
Authors: Wang Zuo , Elekwachi Chijioke O. , Jiao Jinzhen , Wang Min , Tang Shaoxun , Zhou Chuanshe , Tan Zhiliang , Forster Robert J.
Published: March 2017

This study was performed to investigate the initial colonization of metabolically active methanogens and subsequent changes in four fractions: the rumen solid-phase (RS), liquid-phase (RL), protozoa-associated (RP), and epithelium-associated (RE) from 1 to 60 d after birth, and manipulate methanogen community by early weaning on 40 d and supplementing rhubarb from 40 to 60 d in black goats. The RNA-based real-time quantitative PCR and 16S rRNA amplicon sequencing were employed to indicate the metabolically active methanogens. Results showed that active methanogens colonized in RL and RE on 1 d after birth. RP and RE contained the highest and lowest density of methanogens, respectively. Methanobrevibacter, Candidatus Methanomethylophilus, and Methanosphaera were the top three genera. The methanogen communities before weaning differed from those post weaning and the structure of the methanogen community in RE was distinct from those in the other three fractions. The discrepancies in the distribution of methanogens across four fractions, and various fluctuations in abundances among four fractions according to age were observed. The addition of rhubarb significantly (P < 0.05) reduced the abundances of Methanimicrococcus spp. in four fractions on 50 d, but did not change the methanogen community composition on 60 d.
Neural basis of negativity bias in the perception of ambiguous facial expression
Authors: Ito Takehito , Yokokawa Keita , Yahata Noriaki , Isato Ayako , Suhara Tetsuya , Yamada Makiko
Published: March 2017

Negativity bias, which describes the tendency to interpret ambiguous stimuli or events as negative, is often observed in patients with depression and may prevent psychological well-being. Here, we used ambiguous facial stimuli, with negative (sad) and positive (happy) emotions simultaneously accessible, to examine neural activation during perceptual decision-making in healthy participants. The negativity bias was positively correlated with the activity of the bilateral pregenual anterior cingulate cortex (pgACC) when ambiguous faces were perceived as sad versus happy. Additionally, the strength of the functional connectivity between the bilateral pgACC and the right dorsal ACC (dACC)/right thalamus was positively correlated with hopelessness, one of the core characteristics of depression. Given the role of the pgACC as a major site of depressive affect and the roles of the dACC and thalamus in conflict monitoring and vigilance, respectively, our results reveal valid and important neuroanatomical correlates of the association between negativity bias and hopelessness in the healthy individuals.
Comparison of Two Massively Parallel Sequencing Platforms using 83 Single Nucleotide Polymorphisms for Human Identification
Authors: Apaga Dame Loveliness T. , Dennis Sheila E. , Salvador Jazelyn M. , Calacal Gayvelline C. , De Ungria Maria Corazon A.
Published: March 2017

The potential of Massively Parallel Sequencing (MPS) technology to vastly expand the capabilities of human identification led to the emergence of different MPS platforms that use forensically relevant genetic markers. Two of the MPS platforms that are currently available are the MiSeq® FGx™ Forensic Genomics System (Illumina) and the HID-Ion Personal Genome Machine (PGM)™ (Thermo Fisher Scientific). These are coupled with the ForenSeq™ DNA Signature Prep kit (Illumina) and the HID-Ion AmpliSeq™ Identity Panel (Thermo Fisher Scientific), respectively. In this study, we compared the genotyping performance of the two MPS systems based on 83 SNP markers that are present in both MPS marker panels. Results show that MiSeq® FGx™ has greater sample-to-sample variation than the HID-Ion PGM™ in terms of read counts for all the 83 SNP markers. Allele coverage ratio (ACR) values show generally balanced heterozygous reads for both platforms. Two and four SNP markers from the MiSeq® FGx™ and HID-Ion PGM™, respectively, have average ACR values lower than the recommended value of 0.67. Comparison of genotype calls showed 99.7% concordance between the two platforms.
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy
Authors: Chen Cheng-Yu , Fuh Lih-Jyh , Huang Chien-Chung , Hsu Chin-Jung , Su Chen-Ming , Liu Shan-Chi , Lin Yu-Min , Tang Chih-Hsin
Published: March 2017

Cysteine-rich 61 (Cyr61 or CCN1), a secreted protein from the CCN family, is an important proinflammatory cytokine. Migration and infiltration of mononuclear cells to inflammatory sites play a critical role in the pathogenesis of rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1/CCL2) is the key chemokine that regulates migration and infiltration of monocytes. Here, we examined the role of CCN1 in monocyte migration, and CCL2 expression in osteoblasts. We found higher levels of CCN1 and CCL2 in synovial fluid from RA patients compared with levels from non-RA controls. We also found that the CCN1-induced increase in CCL2 expression is mediated by the MAPK signaling pathway and that miR-518a-5p expression was negatively regulated by CCN1 via the MAPK cascade. In contrast, inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA ameliorated articular swelling, cartilage erosion, and infiltration of monocytes in the ankle joints of mice with collagen-induced arthritis. Our study describes how CCN1 promotes monocyte migration by upregulating CCL2 expression in osteoblasts in RA disease. CCN1 could serve as a potential target for RA treatment.
Interspecific differences in how habitat degradation affects escape response
Authors: McCormick Mark I. , Allan Bridie J. M.
Published: March 2017

Degradation of habitats is widespread and a leading cause of extinctions. Our study determined whether the change in the chemical landscape associated with coral degradation affected the way three fish species use olfactory information to optimize their fast-start escape response. Water from degraded coral habitats affected the fast-start response of the three closely-related damselfishes, but its effect differed markedly among species. The Ward’s damselfish (Pomacentrus wardi) was most affected by water from degraded coral, and displayed shorter distances covered in the fast-start and slower escape speeds compared to fish in water from healthy coral. In the presence of alarm odours, which indicate an imminent threat, the Ambon damsel (P. amboinensis) displayed enhanced fast-start performance in water from healthy coral, but not when in water from degraded coral. In contrast, while the white-tailed damsel (P. chrysurus) was similarly primed by its alarm odour, the elevation of fast start performance was not altered by water from degraded coral. These species-specific responses to the chemistry of degraded water and alarm odours suggest differences in the way alarm odours interact with the chemical landscape, and differences in the way species balance information about threats, with likely impacts on the survival of affected species in degraded habitats.
Visualization of weak interactions between quantum dot and graphene in hybrid materials
Authors: Cao Shuo , Wang Jingang , Ding Yong , Sun Mengtao , Ma Fengcai
Published: March 2017

The mechanisms of the weak interactions within hybrid materials such as quantum dot (QD) and graphene (GR) have important implications for the design of related optoelectronic devices. We characterize the weak interactions in hybrid QD-GR systems using a non-covalent interactions approach. For a single Cd13Se13 QD with a core-cage structure, the intensity of the steric repulsive strain in every Cd-Se spatial four-atom ring of the cage surface is stronger than that of the inter-core-cage structure. Van der Waals (vdW) interactions occur within the cavity of the cage and within the six-atom rings of the cage surface. The spatial repulsion strain and attractive interactions play a key role in stabilizing the structure of the monolayer graphene. Interestingly, the spatial six-atom ring of the single QD change into spatial four-atom rings of the QD in the hybrid system, accompanied by the translation of vdW interactions into steric repulsive interactions. We conclude that the vdW interactions with π extensions and the weak attractive interactions within local areas between the QD and graphene together stabilize the integral structure of the hybrid QD-GR system. These results explain of the formation mechanism and the stabilization of the components in QD-GR hybrid materials.
The effects of symmetrical arrangement on quantum metrology
Authors: Jin Yao
Published: March 2017

An obstacle for precision improvement in quantum metrology is the information loss causing by the unavoidable interaction between probe system and environment. Quantum fluctuations are environment no system can be isolated from and it will make the precision of initial parameter estimation of the probe atom decrease with time. After the typical time of the spontaneous decay of the probe atom, the precision is greatly damaged. However, quantum fluctuations can be modified. Our results show that if we put several ancillary atoms beside the probe atom in symmetrical arrangement, the probe atom will be affected by the ancillary atoms indirectly and the information loss of the probe atom causing by the quantum fluctuations will be partially avoided. We find that the retained precision after long time evolution can approaches to $$\tfrac{{\bf{9}}}{{\bf{16}}}$$

9

16

times of the initial precision in condition that the probe atom and three ancillary atoms are located in the vertex of regular tetrahedron.
High performance lithium-sulfur batteries for storing pulsed energy generated by triboelectric nanogenerators
Authors: Song Weixing , Wang Chao , Gan Baoheng , Liu Mengmeng , Zhu Jianxiong , Nan Xihui , Chen Ning , Sun Chunwen , Chen Jitao
Published: March 2017

Storing pulsed energy harvested by triboelectric nanogenerators (TENGs) from ambient mechanical motion is an important technology for obtaining sustainable, low-cost, and green power. Here, we introduce high-energy-density Li-S batteries with excellent performance for storing pulsed output from TENGs. The sandwich-structured sulfur composites with multi-walled carbon nanotubes and polypyrrole serve as cathode materials that suppress the shuttle effect of polysulfides and thus preserve the structural stability of the cathode during Li-ion insertion and extraction. The charging time and energy storage efficiency of the Li-S batteries are directly affected by the rotation rates of the TENGs. The average storage efficiency of the batteries for pulsed output from TENGs can exceed 80% and even reach 93% at low discharge currents. The Li-S batteries also show excellent rate performance for storing pulsed energy at a high discharge current rate of 5 C. The high storage efficiency and excellent rate capability and cyclability demonstrate the feasibility of storing and exploiting pulsed energy provided by TENGs and the potential of Li-S batteries with high energy storage efficiency for storing pulsed energy harvested by TENGs.
Large-scale prediction of microRNA-disease associations by combinatorial prioritization algorithm
Authors: Yu Hua , Chen Xiaojun , Lu Lu
Published: March 2017

Identification of the associations between microRNA molecules and human diseases from large-scale heterogeneous biological data is an important step for understanding the pathogenesis of diseases in microRNA level. However, experimental verification of microRNA-disease associations is expensive and time-consuming. To overcome the drawbacks of conventional experimental methods, we presented a combinatorial prioritization algorithm to predict the microRNA-disease associations. Importantly, our method can be used to predict microRNAs (diseases) associated with the diseases (microRNAs) without the known associated microRNAs (diseases). The predictive performance of our proposed approach was evaluated and verified by the internal cross-validations and external independent validations based on standard association datasets. The results demonstrate that our proposed method achieves the impressive performance for predicting the microRNA-disease association with the Area Under receiver operation characteristic Curve (AUC), 86.93%, which is indeed outperform the previous prediction methods. Particularly, we observed that the ensemble-based method by integrating the predictions of multiple algorithms can give more reliable and robust prediction than the single algorithm, with the AUC score improved to 92.26%. We applied our combinatorial prioritization algorithm to lung neoplasms and breast neoplasms, and revealed their top 30 microRNA candidates, which are in consistent with the published literatures and databases.
Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge
Authors: Pepe Giovanna , Braga Daniele , Renzi Tiziana A. , Villa Alessandro , Bolego Chiara , D’Avila Francesca , Barlassina Cristina , Maggi Adriana , Locati Massimo , Vegeto Elisabetta
Published: March 2017

Beyond the physiology of reproduction, estrogen controls the homeostasis of several tissues. Although macrophages play a key role in tissue remodeling, the interplay with estrogen is still ill defined. Using a transcriptomic approach we first obtained a comprehensive list of genes that are differentially expressed in peritoneal macrophages in response to physiological levels of 17β-estradiol (E2) injected in intact female mice. Our data also showed the dynamic nature of the macrophage response to E2and pointed to specific biological programs induced by the hormone, with cell proliferation, immune response and wound healing being the most prominent functional categories. Indeed, the exogenous administration of E2and, more importantly, the endogenous hormonal surge proved to support macrophage proliferationin vivo, as shown by cell cycle gene expression, BrdU incorporation and cell number. Furthermore, E2promoted an anti-inflammatory and pro-resolving macrophage phenotype, which converged on the induction of genes related to macrophage alternative activation and on IL-10 expressionin vivo. Hormone action was maintained in an experimental model of peritoneal inflammation based on zymosan injection. These findings highlight a direct effect of estrogen on macrophage expansion and phenotypic adaptation in homeostatic conditions and suggest a role for this interplay in inflammatory pathologies.
Gene delivery to Nile tilapia cells for transgenesis and the role of PI3K-c2α in angiogenesis
Authors: Tonelli Fernanda Maria Policarpo , Lacerda Samyra Maria dos Santos Nassif , Procópio Marcela Santos , Lemos Breno Luiz Sales , de França Luiz Renato , Resende Rodrigo Ribeiro
Published: March 2017

Microinjection is commonly performed to achieve fish transgenesis; however, due to difficulties associated with this technique, new strategies are being developed. Here we evaluate the potential of lentiviral particles to genetically modify Nile tilapia cells to achieve transgenesis using three different approaches: spermatogonial stem cell (SSC) genetic modification and transplantation (SC), in vivo transduction of gametes (GT), and fertilised egg transduction (ET). The SC protocol using larvae generates animals with sustained production of modified sperm (80% of animals with 77% maximum sperm fluorescence [MSF]), but is a time-consuming protocol (sexual maturity in Nile tilapia is achieved at 6 months of age). GT is a faster technique, but the modified gamete production is temporary (70% of animals with 52% MSF). ET is an easier way to obtain mosaic transgenic animals compared to microinjection of eggs, but non-site-directed integration in the fish genome can be a problem. In this study, PI3Kc2α gene disruption impaired development during the embryo stage and caused premature death. The manipulator should choose a technique based on the time available for transgenic obtainment and if this generation is required to be continuous or not.
Hepatic mitochondrial dysfunction is a feature of Glycogen Storage Disease Type Ia (GSDIa)
Authors: Farah Benjamin L. , Sinha Rohit A. , Wu Yajun , Singh Brijesh K. , Lim Andrea , Hirayama Masahiro , Landau Dustin J. , Bay Boon Huat , Koeberl Dwight D. , Yen Paul M.
Published: March 2017

Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. The latter leads to steatohepatitis, cirrhosis, and the formation of hepatic adenomas and carcinomas. Currently, little is known about the function of various organelles and their impact on metabolism in GSDIa. Accordingly, we investigated mitochondrial function in cell culture and mouse models of GSDIa. We found impairments in oxidative phosphorylation and changes in TCA cycle metabolites, as well as decreased mitochondrial membrane potential and deranged mitochondrial ultra-structure in these model systems. Mitochondrial content also was decreased, likely secondary to decreased mitochondrial biogenesis. These deleterious effects culminated in the activation of the mitochondrial apoptosis pathway. Taken together, our results demonstrate a role for mitochondrial dysfunction in the pathogenesis of GSDIa, and identify a new potential target for the treatment of this disease. They also provide new insight into the role of carbohydrate overload on mitochondrial function in other hepatic diseases, such as non-alcoholic fatty liver disease.
Raman Sensitive Degradation and Etching Dynamics of Exfoliated Black Phosphorus
Authors: Alsaffar Fadhel , Alodan Sarah , Alrasheed Abdul , Alhussain Abdulrahman , Alrubaiq Noura , Abbas Ahmad , Amer Moh. R.
Published: March 2017

Layered black phosphorus has drawn much attention due to the existence of a band gap compared to the widely known graphene. However, environmental stability of black phosphorus is still a major issue, which hinders the realization of practical device applications. Here, we spatially Raman map exfoliated black phosphorus using confocal fast-scanning technique at different time intervals. We observe a Raman intensity modulation for "Equation missing", B2 g, and "Equation missing" modes. This Raman modulation is found to be caused by optical interference, which gives insights into the oxidation mechanism. Finally, we examine the fabrication compatible PMMA coating as a viable passivation layer. Our measurements indicate that PMMA passivated black phosphorus thin film flakes can stay pristine for a period of 19 days when left in a dark environment, allowing sufficient time for further nanofabrication processing. Our results shed light on black phosphorus degradation which can aid future passivation methods.
Polyphonic sonification of electrocardiography signals for diagnosis of cardiac pathologies
Authors: Kather Jakob Nikolas , Hermann Thomas , Bukschat Yannick , Kramer Tilmann , Schad Lothar R. , Zöllner Frank Gerrit
Published: March 2017

Electrocardiography (ECG) data are multidimensional temporal data with ubiquitous applications in the clinic. Conventionally, these data are presented visually. It is presently unclear to what degree data sonification (auditory display), can enable the detection of clinically relevant cardiac pathologies in ECG data. In this study, we introduce a method for polyphonic sonification of ECG data, whereby different ECG channels are simultaneously represented by sound of different pitch. We retrospectively applied this method to 12 samples from a publicly available ECG database. We and colleagues from our professional environment then analyzed these data in a blinded way. Based on these analyses, we found that the sonification technique can be intuitively understood after a short training session. On average, the correct classification rate for observers trained in cardiology was 78%, compared to 68% and 50% for observers not trained in cardiology or not trained in medicine at all, respectively. These values compare to an expected random guessing performance of 25%. Strikingly, 27% of all observers had a classification accuracy over 90%, indicating that sonification can be very successfully used by talented individuals. These findings can serve as a baseline for potential clinical applications of ECG sonification.
NMR spectroscopy of single sub-nL ova with inductive ultra-compact single-chip probes
Authors: Grisi Marco , Vincent Franck , Volpe Beatrice , Guidetti Roberto , Harris Nicola , Beck Armin , Boero Giovanni
Published: March 2017

Nuclear magnetic resonance (NMR) spectroscopy enables non-invasive chemical studies of intact living matter. However, the use of NMR at the volume scale typical of microorganisms is hindered by sensitivity limitations, and experiments on single intact organisms have so far been limited to entities having volumes larger than 5 nL. Here we show NMR spectroscopy experiments conducted on single intact ova of 0.1 and 0.5 nL (i.e. 10 to 50 times smaller than previously achieved), thereby reaching the relevant volume scale where life development begins for a broad variety of organisms, humans included. Performing experiments with inductive ultra-compact (1 mm2) single-chip NMR probes, consisting of a low noise transceiver and a multilayer 150 μm planar microcoil, we demonstrate that the achieved limit of detection (about 5 pmol of 1H nuclei) is sufficient to detect endogenous compounds. Our findings suggest that single-chip probes are promising candidates to enable NMR-based study and selection of microscopic entities at biologically relevant volume scales.
Identification of mangiferin as a potential Glucokinase activator by structure-based virtual ligand screening
Authors: Min Qiuxia , Cai Xinpei , Sun Weiguang , gao Fei , Li Zhimei , Zhang Qian , Wan Luo-Sheng , Li Hua , Chen Jiachun
Published: March 2017

The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia.
Sets of serum exosomal microRNAs as candidate diagnostic biomarkers for Kawasaki disease
Authors: Jia Hong-Ling , Liu Chao-Wu , Zhang Li , Xu Wei-Jun , Gao Xue-Juan , Bai Jun , Xu Yu-Fen , Xu Ming-Guo , Zhang Gong
Published: March 2017

Although Kawasaki disease is the main cause of acquired heart disease in children, no diagnostic biomarkers are available. We aimed to identify candidate biomarkers for diagnosing Kawasaki disease using serum exosomal microRNAs (miRNAs). Using frozen serum samples from a biobank, high-throughput microarray technologies, two-stage real-time quantitative PCR, and a self-referencing strategy for data normalization, we narrowed down the list of biomarker candidates to a set of 4 miRNAs. We further validated the diagnostic capabilities of the identified miRNAs (namely, CT(miR-1246)-CT(miR-4436b-5p) and CT(miR-197-3p)-CT(miR-671-5p)) in 79 samples from two hospitals. We found that this 4-miRNA set could distinguish KD patients from other febrile patients as well as from healthy individuals in a single pass, with a minimal rate of false positives and negatives. We thus propose, for the first time, that serum exosomal miRNAs represent candidate diagnostic biomarkers for Kawasaki disease. Additionally, we describe an effective strategy of screening for biomarkers of complex diseases even when little mechanistic knowledge is available.
Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions
Authors: Zhang Chen , Jiang Hui , Wang Pin , Liu Heng , Sun Xiulian
Published: March 2017

Mitochondria are intracellular organelles involved in cell survival and death, and dysfunctions of mitochondria are related to neurodegenerative diseases. As the most abundant protein in the mitochondrial inner membrane, adenine nucleotide translocator 1 (ANT1) plays a critical role in mitochondrial function, including the exchange of adenosine triphosphate/adenosine diphosphate (ATP/ADP) in mitochondria, basal proton leak and mitochondrial permeability transition pore (mPTP). Here, we show that ANT1 transcription is regulated by transcription factor NF-kappa B (NF-κB). NF-κB is bound to two NF-κB responsive elements (NREs) located at +1 to +20 bp and +41 to +61 bp in the ANT1 promoter. An NF-κB signalling stimulator, tumour necrosis factor alpha (TNFα), suppresses ANT1 mRNA and protein expression. Activation of NF-κB by TNFα impairs ATP/ADP exchange and decreases ATP production in mitochondria. Activation of NF-κB by TNFα decreases calcium induced mPTP opening, elevates mitochondrial potential and increases reactive oxygen species (ROS) production in both T98G human glioblastoma cells and rat cortical neurons. These results demonstrate that NF-κB signalling may repress ANT1 gene transcription and impair mitochondrial functions.
Biological Activity of Masked Endotoxin
Authors: Schwarz Harald , Gornicec Jan , Neuper Theresa , Parigiani Maria Alejandra , Wallner Michael , Duschl Albert , Horejs-Hoeck Jutta
Published: March 2017

Low endotoxin recovery (LER) is a recently discovered phenomenon describing the inability of limulus amebocyte lysate (LAL)-based assays to detect lipopolysaccharide (LPS) because of a “masking effect” caused by chelators or detergents commonly used in buffer formulations for medical products and recombinant proteins. This study investigates the masking capacities of different buffer formulations and whether masked endotoxin is biologically active. We show that both naturally occurring endotoxin as well as control standard endotoxin can be affected by LER. Furthermore, whereas masked endotoxin cannot be detected in Factor C based assays, it is still detectable in a cell-based TLR4-NF-κB-luciferase reporter gene assay. Moreover, in primary human monocytes, masked LPS induces the expression of pro-inflammatory cytokines and surface activation markers even at very low concentrations. We therefore conclude that masked LPS is a potent trigger of immune responses, which emphasizes the potential danger of masked LPS, as it may pose a health threat in pharmaceutical products or compromise experimental results.
Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System
Authors: Ouyang Mengxing , Hill Winfield , Lee Jung Hyun , Hur Soojung Claire
Published: March 2017

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.
Inhibitory responses mediated by vagal nerve stimulation are diminished in stomachs of mice with reduced intramuscular interstitial cells of Cajal
Authors: Beckett Elizabeth A. H. , Sanders Kenton M. , Ward Sean M.
Published: March 2017

Intramuscular interstitial cells of Cajal (ICC-IM) are closely associated with enteric motor nerve terminals and electrically coupled to smooth muscle cells within the gastric musculature. Previous studies investigating the role of ICC-IM in motor neurotransmission have used indiscriminate electric field stimulation of neural elements within the gastric wall. To determine the role of ICC-IM in transduction of vagally-mediated motor input to gastric muscles electrical and mechanical responses to selective electrical vagal stimulation (EVS) were recorded from gastric fundus and antral regions of wild type and W/WV mice, which lack most ICC-IM. EVS evoked inhibitory junction potentials (IJPs) in wild type muscles that were attenuated or abolished by L-NNA. IJPs were rarely evoked in W/WV muscles by EVS, and not affected by L-NNA. EVS evoked relaxation of wild type stomachs, but the predominant response of W/WV stomachs was contraction. EVS applied after pre-contraction with bethanechol caused relaxation of wild type gastric tissues and these were inhibited by the nitric oxide synthase inhibitor L-NNA. Relaxation responses were of smaller amplitude in W/WV muscles and L-NNA did not attenuate relaxation responses in W/WV fundus muscles. These data suggest an important role for ICC-IM in vagally-mediated nitrergic relaxation in the proximal and distal stomach.
Near-Infrared Photoluminescent Carbon Nanotubes for Imaging of Brown Fat
Authors: Yudasaka Masako , Yomogida Yohei , Zhang Minfang , Tanaka Takeshi , Nakahara Masako , Kobayashi Norihiko , Okamatsu-Ogura Yuko , Machida Ken , Ishihara Kazuhiko , Saeki Kumiko , Kataura Hiromichi
Published: March 2017

Near-infrared photoluminescent single-walled carbon nanotubes (CNTs) are expected to provide effectual bio-imaging tools, although, as yet, only limited applications have been reported. Here, we report that CNTs coated with an amphiphilic and biocompatible polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate; PMB), generate high-quality images of brown fat. Brown fat is a heat-productive adipose tissue, which is attracting increasing attention as a new therapeutic target for obesity-associated metabolic disorders. Its brown colour is mainly attributed to densely packed capillaries, which facilitate its high heat-exchanging efficiency. Currently, positron emission tomography-computed tomography is the only practical technique to identify brown fat distribution in the living body; however, it is expensive to use. By virtue of their high affinity to apolipoproteins and exemption from macrophage phagocytosis, PMB-CNTs selectively accumulate on capillary endothelial cells but not larger vessels in adipose tissue. Therefore, the image brightness of adipose tissue can directly reflect the capillary density, and indirectly the thermogenic capability and brownness. PMB-CNTs provide clearer images than conventional organic dyes, as the high level of transmitted light passes through the body with less light scattering. Thus, PMB-CNT-based imaging methods could open a new phase in thermogenic adipose tissue research.
Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data
Authors: Magombedze Gesham , Shiri Tinevimbo , Eda Shigetoshi , Stabel Judy R.
Published: March 2017

Available diagnostic assays forMycobacterium aviumsubsp.paratuberculosis(MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-γ, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-γ/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.
A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses
Authors: Priye Aashish , Bird Sara W. , Light Yooli K. , Ball Cameron S. , Negrete Oscar A. , Meagher Robert J.
Published: March 2017

Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. Here we demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. Our smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Together, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.
Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation
Authors: Andrio Emilie , Lotte Romain , Hamaoui Daniel , Cherfils Jacqueline , Doye Anne , Daugaard Mads , Sorensen Poul H. , Bost Frédéric , Ruimy Raymond , Mettouchi Amel , Lemichez Emmanuel
Published: March 2017

The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation.
Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy
Authors: Kim Ganghun , Nagarajan Naveen , Pastuzyn Elissa , Jenks Kyle , Capecchi Mario , Shepherd Jason , Menon Rajesh
Published: March 2017

Here we demonstrate widefield (field diameter = 200 μm) fluorescence microscopy and video imaging inside the rodent brain at a depth of 2 mm using a simple surgical glass needle (cannula) of diameter 0.22 mm as the primary optical element. The cannula guides excitation light into the brain and the fluorescence signal out of the brain. Concomitant image-processing algorithms are utilized to convert the spatially scrambled images into fluorescent images and video. The small size of the cannula enables minimally invasive imaging, while the long length (>2 mm) allow for deep-brain imaging with no additional complexity in the optical system. Since no scanning is involved, widefield fluorescence video at the native frame rate of the camera can be achieved.