bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroimaging and the Neuroanatomy of Posttraumatic Stress Disorder
Authors: Rauch Scott L. , Shin Lisa M. , Whalen Paul J. , Pitman Roger K.
Published: April 2016

Contemporary neuroimaging methods have been used to gather initial data regarding the neural substrates of posttraumatic stress disorder (PTSD). Morphometric magnetic resonance imaging (MRI) studies have reliably shown reduced hippocampal volume in subjects with PTSD vs control cohorts. Functional imaging studies have implicated a network of brain regions in PTSD, comprising the amygdala, hippocampus, and anterior paralimbic territories (including anterior cingulate cortex), as well as Broca's area and visual cortex. Extant relevant neuroimaging data are reviewed, and a tentative heuristic neuroanatomical model of PTSD is provided. In conclusion, emerging strategies for advancement in this field are outlined.
Vocabulary does not equal language, but neither does morphosyntax
Authors: GRÜTER THERES
Published: April 2016

The study of bilingual development has been, and must be, an interdisciplinary endeavor; Carroll (Carroll) presents us with a perspective from within one particular discipline, that of generative linguistics. From this vantage point, she provides us perhaps most importantly with the reminder that language is not a unitary construct, and cautions against extrapolating from findings on the learning of one particular aspect of language, such as vocabulary, to language acquisition more broadly. I wholeheartedly agree (for a similar point, see Paradis & Grüter, 2014). I do not agree, however, with Carroll's implication that such unwarranted extrapolation is characteristic of current research on input and bilingual development. A number of recent studies have looked specifically at the differential relation between input (in a wide sense) and bilingual children's acquisition of different linguistic phenomena. Unsworth (2014), for example, reported different effects of input variation on Dutch–English bilingual children's acquisition of grammatical gender versus indefinite object scrambling.
Individual emergency physician admission rates: predictably unpredictable
Authors: Mutrie David , Bailey S. Kathleen , Malik Saleem
Published: April 2016

Objective:

We sought to determine the degree and possible causes of variability in admission practices among individual emergency physicians (EPs) at 1 emergency department (ED) using a Canadian Emergency Department Triage Acuity Scale (CTAS)–matched ED patient population.

Methods:

We distributed a survey measuring attitudes and demographics to all EPs (n= 30) at a large regional hospital. Hospital admissions data from 1 calendar year were matched to individual EP survey results. Emergency physicians were ranked as “lower,” “average” or “higher” admitters and, using these categorical variables, the data set was analyzed for correlations and trends.

Results:

Overall, 97.0% of the EPs responded to the survey. Admissions by EPs ranged from 8.7% to 17.0%, (mean 12.52, standard deviation [SD] 2.21) of all patients seen. CTAS category–specific admission data demonstrated variability in the admission ranking of individual EPs. No EPs consistently performed at any 1 admission ranking across all CTAS categories. More years of emergency medicine experience was significantly correlated with higher admissions in the CTAS-2 ranking (r= 0.4,p< 0.05). Whether a physician worked full-time, part-time or as a locum was not associated with patterns of admission, nor was any particular postgraduate certification (e.g., CCFP, CCFP EM, FRCPC) or any of the surveyed attitudinal traits.

Conclusion:

Individual EPs' overall and CTAS-specific admissions varied substantially, and followed an approximately normal distribution curve. Emergency physicians with more years of experience had a statistically higher CTAS-2 admission rate; however, other variables, including postgraduate certification status, decision-related attitudes toward admission, and reported practices were not associated with admission proportions. Emergency physicians tend to have uniquely individual admission ranking profiles across all the CTAS categories.
Regional self-reliance for livestock feed, meat, dairy and eggs in the Northeast USA
Authors: Conrad Zach , Tichenor Nicole E. , Peters Christian J. , Griffin Timothy S.
Published: April 2016

The production of livestock feed in the USA is geographically concentrated, which poses several risks. Extreme weather events and disease outbreaks have the potential to disrupt production in these areas, which could reduce the national output of meat, dairy and eggs. Additionally, geographically concentrated livestock and feed production systems have been observed to contribute excessive nutrient loads to surrounding soil and water bodies, thereby threatening environmental sustainability. Geographic relocation of production systems has been proposed as an adaptation strategy to increase system resilience and this could take the shape of more geographically dispersed livestock feed production. We estimate the degree to which the demand for meat, dairy and eggs in the Northeast region is met with current levels of regional feed and livestock production, a term that we refer to as regional self-reliance. We combine mean annual (2001–2010) data on Northeast regional land use; crop output; meat, dairy and egg output; and food consumption with a livestock feed requirements model. An annual mean of over 6.1 million ha of land in the Northeast was dedicated to livestock feed from 2001 to 2010, with nearly 80% located in just three states (Pennsylvania, New York and West Virginia). The region is a net importer of livestock feed (in terms of total digestible nutrients and crude protein), as well as meat, dairy and eggs (in terms of total human-edible energy and protein). This is the result of a confluence of long-term regional trends that include the movement of agricultural production out of the region with a concomitant increase in the regional population and an increase in the national demand for meat, dairy and eggs. Limited slaughter output in the region is a key limiting factor to increasing the region's self-reliance for livestock products.
Aperture-coupled ESPAR antenna with unique feed network for symmetric switched beam radiation patterns
Authors: Umair Hassan , Muhammad Niaz , Hassan Tayyab , Rashid Imran , Bhatti Farooq A.
Published: April 2016

Aperture-coupled ESPAR antenna with a unique feed structure for switched beam application has been presented. The feed structure provides control over surface current of the driven element with the help of which main lobe can be steered in desired direction. This control has been achieved through the use of PIN-diodes. Finite element method has been utilized for design and simulated and measured results have been presented for validation. The antenna has the ability to steer the main beam in six directions. All radiation patterns are symmetric. The planar aperture-coupled nature of proposed antenna is ideal for integration and commercialization.
Design and analysis of miniaturized UWB antenna with tunable notched band
Authors: Sharma Priyanka , Vyas Kirti , Yadav Rajendra Prasad
Published: April 2016

We report in this paper a novel miniaturized (12 × 18 × 1.6 mm3) microstrip fed UWB antenna with tunable notched band characteristics. The proposed antenna covers the tunable notched band for IEEE 802.11a wireless local area network operating in the frequency band of 5.15–5.825 GHz. The design of proposed antenna includes annular ring radiating patch with two T-shaped strips present inside it. The band notching is obtained by adjusting coupling between T-shaped strips placed inside the annular ring. In order to achieve larger bandwidth the ground plane of the microstrip antenna is modified. The simulated return loss of the proposed antenna has been verified in fabricated antenna experimentally, which has been in good agreement.
Risky Integration
Authors: Fulginiti Anthony , Rice Eric , Hsu Hsun-Ta , Rhoades Harmony , Winetrobe Hailey
Published: April 2016

Abstract. Background: Although the protective value of social connectedness is emphasized in suicide prevention programming, little is known about the relationship between connectedness in high-risk runaway and homeless youth (RHY) networks and suicidal ideation. Aims: The study examined how social connectedness, in the form of social network position and network exposures, was associated with suicidal ideation among RHY. Method: Using population-level social network data from 384 RHY, each youth’s network position and exposure to potentially suicidogenic peer attributes were calculated. Logistic regression analyses were used to examine associations between network position (core vs. periphery), peer exposures (e.g., depressed or suicidal peers), and suicidal ideation. Results: In univariable analyses, being in the core of the network and being connected to greater proportions of depressed and suicidal peers increased the likelihood of suicidal ideation. In the final multivariable model, higher exposure to depressed peers remained associated with suicidal ideation, and a marginal effect for network position was observed. Conclusion: The risk of suicidal ideation was linked to depression among peers and to a lesser extent being more integrated into the RHY network. Identifying and treating depression in naturally occurring friendship groups, particularly in the core of the network, represents a promising network-level intervention.
PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila
Authors: Huang Z , Ren S , Jiang Y , Wang T
Published: April 2016

Calcium has an important role in regulating numerous cellular activities. However, extremely high levels of intracellular calcium can lead to neurotoxicity, a process commonly associated with degenerative diseases. Despite the clear role of calcium cytotoxicity in mediating neuronal cell death in this context, the pathological mechanisms remain controversial. We used a well-established Drosophila model of retinal degeneration, which involves the constitutively active TRPP365 channels, to study calcium-induced neurotoxicity. We found that the disruption of mitochondrial function was associated with the degenerative process. Further, increasing autophagy flux prevented cell death in TrpP365 mutant flies, and this depended on the PINK1/Parkin pathway. In addition, the retinal degeneration process was also suppressed by the coexpression of PINK1 and Parkin. Our results provide genetic evidence that mitochondrial dysfunction has a key role in the pathology of cellular calcium neurotoxicity. In addition, the results demonstrated that maintaining mitochondrial homeostasis via PINK1/Parkin-dependent mitochondrial quality control can potentially alleviate cell death in a wide range of neurodegenerative diseases.
Targeting the epigenetics of the DNA damage response in breast cancer
Authors: Montenegro M F , González-Guerrero R , Sánchez-del-Campo L , Piñero-Madrona A , Cabezas-Herrera J , Rodríguez-López J N
Published: April 2016

Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Because the epigenetic factors involved in the DNA damage response are regulated by multiple elements, therapies to target specific components of the epigenetic machinery can be inefficient. In contrast, therapies aimed at inhibiting the methionine cycle can indirectly inhibit both DNA and protein methylation, and the wide variety of genes and pathways that are affected by these methylations make this global strategy very attractive. In the present study, we propose an adjuvant therapy that targets the epigenetics of the DNA damage response in breast cancer cells and that results in efficient apoptosis and a reduction in distant metastases in vivo. We observed that a combined therapy designed to uncouple adenosine metabolism using dipyridamole in the presence of a new synthetic antifolate, 3-O-(3,4,5-trimethoxybenzoyl)-(−)-catechin, simultaneously and efficiently blocked both the folic cycle and the methionine cycle in breast cancer cells and sensitized these cells to radiotherapy. The treatment impeded the recruitment of 53BP1 and BRCA1 to the chromatin regions flanking DNA double-strand breaks and thereby avoided the DNA damage responses in breast cancer cells that were exposed to ionizing radiation. In addition, this hypomethylating therapy was also efficient in reducing the self-renewal capability of breast cancer-initiating cells and induced reversion of mesenchymal phenotypes in breast cancer cells.
β-Arrestins promote podocyte injury by inhibition of autophagy in diabetic nephropathy
Authors: Liu J , Li Q X , Wang X J , Zhang C , Duan Y Q , Wang Z Y , Zhang Y , Yu X , Li N J , Sun J P , Yi F
Published: April 2016

β-Arrestins are multifunctional proteins originally identified as negative adaptors of G protein-coupled receptors (GPCRs). Emerging evidence has also indicated that β-arrestins can activate signaling pathways independent of GPCR activation. This study was to elucidate the role of β-arrestins in diabetic nephropathy (DN) and hypothesized that β-arrestins contribute to diabetic renal injury by mediating podocyte autophagic process. We first found that both β-arrestin-1 and β-arrestin-2 were upregulated in the kidney from streptozotocin-induced diabetic mice, diabetic db/db mice and kidney biopsies from diabetic patients. We further revealed that either β-arrestin-1 or β-arrestin-2 deficiency (Arrb1−/− or Arrb2−/−) ameliorated renal injury in diabetic mice. In vitro, we observed that podocytes increased both β-arrestin-1 and β-arrestin-2 expression levels under hyperglycemia condition and further demonstrated that β-arrestin-1 and β-arrestin-2 shared common mechanisms to suppress podocyte autophagy by negative regulation of ATG12–ATG5 conjugation. Collectively, this study for the first time demonstrates that β-arrestin-1 and β-arrestin-2 mediate podocyte autophagic activity, indicating that β-arrestins are critical components of signal transduction pathways that link renal injury to reduce autophagy in DN. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with DN.
The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration
Authors: Hall A E , Lu W-T , Godfrey J D , Antonov A V , Paicu C , Moxon S , Dalmay T , Wilczynska A , Muller P A J , Bushell M
Published: April 2016

The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.
Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures
Authors: Crudden Cathleen M. , Ziebenhaus Christopher , Rygus Jason P. G. , Ghozati Kazem , Unsworth Phillip J. , Nambo Masakazu , Voth Samantha , Hutchinson Marieke , Laberge Veronique S. , Maekawa Yuuki , Imao Daisuke
Published: April 2016

The Suzuki–Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp2-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki–Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds.
Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
Authors: Dankwa Selasi , Lim Caeul , Bei Amy K. , Jiang Rays H. Y. , Abshire James R. , Patel Saurabh D. , Goldberg Jonathan M. , Moreno Yovany , Kono Maya , Niles Jacquin C. , Duraisingh Manoj T.
Published: April 2016

Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways.
Serial interactome capture of the human cell nucleus
Authors: Conrad Thomas , Albrecht Anne-Susann , de Melo Costa Veronica Rodrigues , Sauer Sascha , Meierhofer David , Ørom Ulf Andersson
Published: April 2016

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present ‘serial RNA interactome capture’ (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)–RNA–protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA–RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.
4D Visualization of replication foci in mammalian cells corresponding to individual replicons
Authors: Chagin V. O. , Casas-Delucchi C. S. , Reinhart M. , Schermelleh L. , Markaki Y. , Maiser A. , Bolius J. J. , Bensimon A. , Fillies M. , Domaing P. , Rozanov Y. M. , Leonhardt H. , Cardoso M. C.
Published: April 2016

Since the pioneering proposal of the replicon model of DNA replication 50 years ago, the predicted replicons have not been identified and quantified at the cellular level. Here, we combine conventional and super-resolution microscopy of replication sites in live and fixed cells with computational image analysis. We complement these data with genome size measurements, comprehensive analysis of S-phase dynamics and quantification of replication fork speed and replicon size in human and mouse cells. These multidimensional analyses demonstrate that replication foci (RFi) in three-dimensional (3D) preserved somatic mammalian cells can be optically resolved down to single replicons throughout S-phase. This challenges the conventional interpretation of nuclear RFi as replication factories, that is, the complex entities that process multiple clustered replicons. Accordingly, 3D genome organization and duplication can be now followed within the chromatin context at the level of individual replicons.
Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models
Authors: Parsons Matthew P. , Vanni Matthieu P. , Woodard Cameron L. , Kang Rujun , Murphy Timothy H. , Raymond Lynn A.
Published: April 2016

It has become well accepted that Huntington disease (HD) is associated with impaired glutamate uptake, resulting in a prolonged time-course of extracellular glutamate that contributes to excitotoxicity. However, the data supporting this view come largely from work in synaptosomes, which may overrepresent nerve-terminal uptake over astrocytic uptake. Here, we quantify real-time glutamate dynamics in HD mouse models by high-speed imaging of an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) and electrophysiological recordings of synaptically activated transporter currents in astrocytes. These techniques reveal a disconnect between the results obtained in synaptosomes and those in situ. Exogenous glutamate uptake is impaired in synaptosomes, whereas real-time measures of glutamate clearance in the HD striatum are normal or even accelerated, particularly in the aggressive R6/2 model. Our results highlight the importance of quantifying glutamate dynamics under endogenous release conditions, and suggest that the widely cited uptake impairment in HD does not contribute to pathogenesis.
Chemical ordering suppresses large-scale electronic phase separation in doped manganites
Authors: Zhu Yinyan , Du Kai , Niu Jiebin , Lin Lingfang , Wei Wengang , Liu Hao , Lin Hanxuan , Zhang Kai , Yang Tieying , Kou Yunfang , Shao Jian , Gao Xingyu , Xu Xiaoshan , Wu Xiaoshan , Dong Shuai , Yin Lifeng , Shen Jian
Published: April 2016

For strongly correlated oxides, it has been a long-standing issue regarding the role of the chemical ordering of the dopants on the physical properties. Here, using unit cell by unit cell superlattice growth technique, we determine the role of chemical ordering of the Pr dopant in a colossal magnetoresistant (La1−yPry)1−xCaxMnO3 (LPCMO) system, which has been well known for its large length-scale electronic phase separation phenomena. Our experimental results show that the chemical ordering of Pr leads to marked reduction of the length scale of electronic phase separations. Moreover, compared with the conventional Pr-disordered LPCMO system, the Pr-ordered LPCMO system has a metal–insulator transition that is ∼100 K higher because the ferromagnetic metallic phase is more dominant at all temperatures below the Curie temperature.
Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis
Authors: Vayndorf Elena M , Scerbak Courtney , Hunter Skyler , Neuswanger Jason R , Toth Marton , Parker J Alex , Neri Christian , Driscoll Monica , Taylor Barbara E
Published: April 2016

Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin–proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded Htt expression, whereas ALM neurons with polyQ-expanded Htt accumulate extended outgrowths and other soma abnormalities. Furthermore, knockdown of genes important for ubiquitin-mediated degradation, lysosomal function, and autophagy modulated these age-related morphological changes in otherwise normal neurons. Our results show that the expression of misfolded proteins in neurodegenerative disease such as Huntington’s disease modifies the morphological remodeling that is normally associated with neuronal aging. Our results also show that morphological remodeling of healthy neurons during aging can be regulated by the UPS and other proteostasis pathways. Collectively, our data highlight a model in which morphological remodeling during neuronal aging is strongly affected by disrupted proteostasis and expression of disease-associated, misfolded proteins such as human polyQ-Htt species.
Critical controllability in proteome-wide protein interaction network integrating transcriptome
Authors: Ishitsuka Masayuki , Akutsu Tatsuya , Nacher Jose C.
Published: April 2016

Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development.
3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant-Impregnated Surfaces
Authors: Kajiya Tadashi , Schellenberger Frank , Papadopoulos Periklis , Vollmer Doris , Butt Hans-Jürgen
Published: April 2016

Condensation of water from the atmosphere on a solid surface is an ubiquitous phenomenon in nature and has diverse technological applications, e.g. in heat and mass transfer. We investigated the condensation kinetics of water drops on a lubricant-impregnated surface, i.e., a micropillar array impregnated with a non-volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. Different stages of condensation can be discriminated. On a lubricant-impregnated hydrophobic micropillar array these are: (1) Nucleation on the lubricant surface. (2) Regular alignment of water drops between micropillars and formation of a three-phase contact line on a bottom of the substrate. (3) Deformation and bridging by coalescence which eventually leads to a detachment of the drops from the bottom substrate. The drop-substrate contact does not result in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated hydrophilic micropillar array, the condensed water drops replace the lubricant. Consequently, the surface loses its slippery property. Our results demonstrate that a Wenzel-like to Cassie transition, required to maintain the facile removal of condensed water drops, can be induced by well-chosen surface hydrophobicity.
A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host
Authors: Rai Pradeep K , Chodisetti Sathi Babu , Nadeem Sajid , Maurya Sudeep K , Gowthaman Uthaman , Zeng Weiguang , Janmeja Ashok K , Jackson David C , Agrewala Javed N
Published: April 2016

Regardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5 million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill Mtb by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of Mtb and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in Mtb infected animals. The mechanism involved was through enhancement of IFN-γ+TNF-α+ polyfunctional Th1 cells and IL-17A+IFN-γ+ Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against Mtb. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.
Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain Cooperation
Authors: Wu Junhui , Balliet Daniel , Van Lange Paul A. M.
Published: April 2016

Prior theory suggests that reputation spreading (e.g., gossip) and punishment are two key mechanisms to promote cooperation in groups, but no behavioral research has yet examined their relative effectiveness and efficiency in promoting and maintaining cooperation. To examine these issues, we observed participants interacting in a four-round public goods game (PGG) with or without gossip and punishment options and a subsequent two-round trust game (TG). We manipulated gossip as the option to send notes about other group members to these members’ future partners and punishment as the option to assign deduction points to reduce other group members’ outcomes with a fee-to-fine ratio of 1:3. Findings revealed that in the four-round PGG, the option to gossip increased both cooperation and individual earnings, whereas the option to punish had no overall effect on cooperation (but a positive effect on cooperation in the last two rounds of the PGG) and significantly decreased individual earnings. Importantly, the initial option to gossip made people more trusting and trustworthy in the subsequent TG when gossip was no longer possible, compared to the no-gossip condition. Thus, we provide some initial evidence that gossip may be more effective and efficient than punishment to promote and maintain cooperation.
Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions
Authors: Huang Yi-Jen , Chao Shih-Chun , Lien Der-Hsien , Wen Cheng-Yen , He Jr-Hau , Lee Si-Chen
Published: April 2016

The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<±1 V) and self-compliance to current up to 50 μA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device.
Optical Magnetic Induction Tomography of the Heart
Authors: Marmugi Luca , Renzoni Ferruccio
Published: April 2016

Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology.
Protein single-model quality assessment by feature-based probability density functions
Authors: Cao Renzhi , Cheng Jianlin
Published: April 2016

Protein quality assessment (QA) has played an important role in protein structure prediction. We developed a novel single-model quality assessment method–Qprob. Qprob calculates the absolute error for each protein feature value against the true quality scores (i.e. GDT-TS scores) of protein structural models and uses them to estimate its probability density distribution for quality assessment. Qprob has been blindly tested on the 11th Critical Assessment of Techniques for Protein Structure Prediction (CASP11) as MULTICOM-NOVEL server. The official CASP result shows that Qprob ranks as one of the top single-model QA methods. In addition, Qprob makes contributions to our protein tertiary structure predictor MULTICOM, which is officially ranked 3rd out of 143 predictors. The good performance shows that Qprob is good at assessing the quality of models of hard targets. These results demonstrate that this new probability density distribution based method is effective for protein single-model quality assessment and is useful for protein structure prediction. The webserver of Qprob is available at: http://calla.rnet.missouri.edu/qprob/. The software is now freely available in the web server of Qprob.
Finding Communities by Their Centers
Authors: Chen Yan , Zhao Pei , Li Ping , Zhang Kai , Zhang Jie
Published: April 2016

Detecting communities or clusters in a real-world, networked system is of considerable interest in various fields such as sociology, biology, physics, engineering science, and interdisciplinary subjects, with significant efforts devoted in recent years. Many existing algorithms are only designed to identify the composition of communities, but not the structures. Whereas we believe that the local structures of communities can also shed important light on their detection. In this work, we develop a simple yet effective approach that simultaneously uncovers communities and their centers. The idea is based on the premise that organization of a community generally can be viewed as a high-density node surrounded by neighbors with lower densities, and community centers reside far apart from each other. We propose so-called “community centrality” to quantify likelihood of a node being the community centers in such a landscape, and then propagate multiple, significant center likelihood throughout the network via a diffusion process. Our approach is an efficient linear algorithm, and has demonstrated superior performance on a wide spectrum of synthetic and real world networks especially those with sparse connections amongst the community centers.
Conditional Deletion of Fgfr3 in Chondrocytes leads to Osteoarthritis-like Defects in Temporomandibular Joint of Adult Mice
Authors: Zhou Siru , Xie Yangli , Li Wei , Huang Junlan , Wang Zuqiang , Tang Junzhou , Xu Wei , Sun Xianding , Tan Qiaoyan , Huang Shuo , Luo Fengtao , Xu Meng , Wang Jun , Wu Tingting , chen Liang , Chen Hangang , Su Nan , Du Xiaolan , Shen Yue , Chen Lin
Published: April 2016

Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a common degenerative disease in adult, which is characterized by progressive destruction of the articular cartilage. To investigate the role of FGFR3 in the homeostasis of TMJ cartilage during adult stage, we generated Fgfr3f/f; Col2a1-CreERT2 (Fgfr3 cKO) mice, in which Fgfr3 was deleted in chondrocytes at 2 months of age. OA-like defects were observed in Fgfr3 cKO TMJ cartilage. Immunohistochemical staining and quantitative real-time PCR analyses revealed a significant increase in expressions of COL10, MMP13 and AMAMTS5. In addition, there was a sharp increase in chondrocyte apoptosis at the Fgfr3 cKO articular surface, which was accompanied by a down-regulation of lubricin expression. Importantly, the expressions of RUNX2 and Indian hedgehog (IHH) were up-regulated in Fgfr3 cKO TMJ. Primary Fgfr3 cKO chondrocytes were treated with IHH signaling inhibitor, which significantly reduced expressions of Runx2, Col10, Mmp13 and Adamts5. Furthermore, the IHH signaling inhibitor partially alleviated OA-like defects in the TMJ of Fgfr3 cKO mice, including restoration of lubricin expression and improvement of the integrity of the articular surface. In conclusion, our study proposes that FGFR3/IHH signaling pathway plays a critical role in maintaining the homeostasis of TMJ articular cartilage during adult stage.
Behavioral and neural correlates of self-referential processing deficits in bipolar disorder
Authors: Zhao Yanli , Luo Wenbo , Chen Jingxu , Zhang Dandan , Zhang Ligang , Xiao Chunling , Fan Fengmei , Zhu Xiaolin , Fan Hongzhen , Tan Shuping
Published: April 2016

Self-referential processing is a core component of social cognition. However, few studies have focused on whether self-referential processing deficits present in bipolar disorder. The current study combined a high-time-resolution event-related potential (ERP) technique with the self-referential memory (SRM) task to evaluate self-referential processing in 23 bipolar patients and 27 healthy controls. All subjects showed a reliable SRM effect, but the bipolar group had poorer recognition scores for the self- and other-referential conditions. The bipolar group presented with smaller voltages in both the self- and other-referential conditions for the N1 (150–220 ms) and the P2 components (130–320 ms) but larger voltages in the positive slow wave (600–1600 ms) component. Larger P3 amplitudes were elicited in the self-referential condition compared with the other-referential condition in controls but not in bipolar patients. Additionally, non-psychotic bipolar patients had a comparative normal SRM effect which was abolished in psychotic bipolar patients; non-psychotic bipolar patients had larger amplitudes of the positive slow wave than the normal controls, whereas it was not differed between psychotic bipolar patients and the healthy subjects. The present study suggests that self- and other-referential processing is impaired in bipolar patients and the deficits may be more pronounced in psychotic bipolar patients.
Proton mediated control of biochemical reactions with bioelectronic pH modulation
Authors: Deng Yingxin , Miyake Takeo , Keene Scott , Josberger Erik E. , Rolandi Marco
Published: April 2016

In Nature, protons (H+) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase and voltage-regulated H+ channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H+ currents and H+ concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H+ between PdHx contacts and solution. The present transducer records bistable pH modulation from an “enzymatic flip-flop” circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. The transducer also controls bioluminescence from firefly luciferase by affecting solution pH.
Differential coding of uncertain reward in rat insular and orbitofrontal cortex
Authors: Jo Suhyun , Jung Min Whan
Published: April 2016

Anterior insular and orbitofrontal cortex (AIC and OFC, respectively) are known to play important roles in decision making under risk. However, risk-related AIC neural activity has not been investigated and it is controversial whether the rodent OFC conveys genuine risk signals. To address these issues, we examined AIC and OFC neuronal activity in rats responding to five distinct auditory cues predicting water reward with different probabilities. Both structures conveyed significant neural signals for reward, value and risk, with value and risk signals conjunctively coded. However, value signals were stronger and appeared earlier in the OFC, and many risk-coding OFC neurons responded only to the cue predicting certain (100%) reward. Also, AIC neurons tended to increase their activity for a prolonged time following a negative outcome and according to previously expected value. These results show that both the AIC and OFC convey neural signals related to reward uncertainty, but in different ways. The OFC might play an important role in encoding certain reward-biased, risk-modulated subjective value, whereas the AIC might convey prolonged negative outcome and disappointment signals.
An insight in magnetic field enhanced zero-valent iron/H2O2 Fenton-like systems: Critical role and evolution of the pristine iron oxides layer
Authors: Xiang Wei , Zhang Beiping , Zhou Tao , Wu Xiaohui , Mao Juan
Published: April 2016

This study demonstrated the synergistic degradation of 4-chlorophenol (4-CP) achieved in a magnetic field (MF) enhanced zero-valent iron (ZVI)/H2O2 Fenton-like (FL) system and revealed an interesting correlative dependence relationship between MF and the pristine iron oxides layer (FexOy) on ZVI particles. First, a comparative investigation between the FL and MF-FL systems was conducted under different experimental conditions. The MF-FL system could suppress the duration of initial lag degradation phase one order of magnitude in addition of the significant enhancement in overall 4-CP degradation. Monitoring of intermediates/products indicated that MF would just accelerate the Fenton reactions to produce hydroxyl radical more rapidly. Evolutions of simultaneously released dissolved iron species suggested that MF would not only improve mass-transfer of the initial heterogeneous reactions, but also modify the pristine ZVI surface. Characterizations of the specific prepared ZVI samples evidenced that MF would induce a special evolution mechanism of the ZVI particles surface depending on the existence of FexOy layer. It comprised of an initial rapid point dissolution of FexOy and a following pitting corrosion of the exposed Fe0 reactive sites, finally leading to appearance of a particular rugged surface topography with numerous adjacent Fe0 pits and FexOy tubercles.
Association between TP53 Arg72Pro polymorphism and leukemia risk: a meta-analysis of 14 case-control studies
Authors: Tian Xin , Dai Shundong , Sun Jing , Jiang Shenyi , Jiang Youhong
Published: April 2016

The relationship between the TP53 Arg72Pro polymorphism (rs1042522) and the risk of leukemia remains controversial. Consequently, we performed a meta-analysis to accurately evaluate the association between TP53 Arg72Pro polymorphism and leukemia risk. A comprehensive search was conducted to find all eligible studies of TP53 Arg72Pro polymorphism and leukemia risk. Fourteen case-control studies, with 2,506 cases and 4,386 controls, were selected for analysis. The overall data failed to indicate a significant association between TP53 Arg72Pro polymorphism and the risk of leukemia (C vs. G: OR = 1.09, 95% CI = 0.93–1.26; CC vs. GC + GG: OR = 1.23, 95% CI = 0.96–1.57). In a subgroup analysis of clinical types, an increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (CC vs. GC + GG: OR = 1.73; 95% CI = 1.07–2.81) but not in the acute myeloid leukemia (AML) subgroup. In the subgroup analysis, no significant associations with ethnicity and the source of the controls were observed. In conclusion, the results suggest that there is no association between TP53 Arg72Pro polymorphism and the risk of leukemia, but the CC genotype may increase the risk of ALL TP53 Arg72Pro polymorphism CC genotype may increase the risk of ALL but is not associated with AML. Further large-scale, well-designed studies are needed to confirm our results.
A deformation energy-based model for predicting nucleosome dyads and occupancy
Authors: Liu Guoqing , Xing Yongqiang , Zhao Hongyu , Wang Jianying , Shang Yu , Cai Lu
Published: April 2016

Nucleosome plays an essential role in various cellular processes, such as DNA replication, recombination and transcription. Hence, it is important to decode the mechanism of nucleosome positioning and identify nucleosome positions in the genome. In this paper, we present a model for predicting nucleosome positioning based on DNA deformation, in which both bending and shearing of the nucleosomal DNA are considered. The model successfully predicted the dyad positions of nucleosomes assembledin vitroand thein vitromap of nucleosomes inSaccharomyces cerevisiae. Applying the model toCaenorhabditis elegansandDrosophila melanogaster, we achieved satisfactory results. Our data also show that shearing energy of nucleosomal DNA outperforms bending energy in nucleosome occupancy prediction and the ability to predict nucleosome dyad positions is attributed to bending energy that is associated with rotational positioning of nucleosomes.
Electronic and magnetic properties of Co doped MoS2 monolayer
Authors: Wang Yiren , Li Sean , Yi Jiabao
Published: April 2016

First principle calculations are employed to calculate the electronic and magnetic properties of Co doped MoS2 by considering a variety of defects including all the possible defect complexes. The results indicate that pristine MoS2 is nonmagnetic. The materials with the existence of S vacancy or Mo vacancy alone are non-magnetic either. Further calculation demonstrates that Co substitution at Mo site leads to spin polarized state. Two substitutional CoMo defects tend to cluster and result in the non-magnetic behaviour. However, the existence of Mo vacancies leads to uniform distribution of Co dopants and it is energy favourable with ferromagnetic coupling, resulting in an intrinsic diluted magnetic semiconductor.