bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Personality and Psychopathology in Patients With Psoriasis
Authors: Vari Chiara , Velotti Patrizia , Crisi Alessandro , Carlesimo Silvana , Richetta Antonio G. , Cesare Zavattini Giulio
Published: December 2017

Abstract. A broad range of literature reported higher rates of psychopathology and personality disorders among patients affected by skin conditions. Specifically, depression, anxiety, and suicidal ideations are more frequently reported by patients affected by skin diseases. This study aimed to examine psychopathology and personality in a group of patients affected by psoriasis by means of a self-report measure (Millon Clinical Multiaxial Inventory – MCMI-III) and a performance-based technique (Wartegg Drawing Completion Test [WDCT], CWS). Study results showed a higher rate of passive-aggressiveness and paranoia among psoriatic patients (MCMI-III). When assessing patients through the performance-based technique (WDCT, CWS), a higher rate of global rejection (GR) – linked by previous literature to suicidal ideation – and a lower affective quality of the drawings emerged. We discuss the clinical importance of detecting psychological issues in dermatology patients by means of a multimethod assessment that goes beyond patients’ self-evaluation of their symptoms and emotions.
Conservative Ideological Shift Among Adolescents in Response to System Threat
Authors: van der Toorn Jojanneke , Jost John T. , Loffredo Benjamin
Published: December 2017

Abstract. We examined conservative ideological shift among adolescents by assessing the effect of different types of threat on the self-reported political orientation of 183 New York City high school students and investigated the mediating role of system justification. Participants read one of three newspaper passages: (1) a system-related passage that described flaws in the American social, economic, and political system; (2) a self-related passage that described the deleterious health effects of cell phone use; or (3) a control passage that described house plant cultivation. Participants then completed measures of system justification and political orientation. As hypothesized, a threat to the system (but not the self) increased self-reported conservatism indirectly through its effect on system justification. This suggests that when the overarching social system is threatened, adolescents may be drawn to conservative ideology and that this is attributable, at least in part, to a heightened desire to defend and bolster the societal status quo.
Parental Perceptions of Emotional and Behavioral Difficulties Among Prepubertal Gender-Nonconforming Children
Authors: Chen Diane , Hidalgo Marco A. , Garofalo Robert
Published: December 2017

The purpose of this study was to better understand parents’ perceptions of how, if at all, their transgender and gender-nonconforming (TGNC) children exhibited common childhood emotional and behavioral concerns in relation to gender nonconformity/gender dysphoria (GD), and to identify ways in which evidence-based interventions (EBI) targeting emotional and behavioral concerns could be adapted to best serve TGNC children. Qualitative data were gathered from a targeted focus group activity with 40 parents (25 mothers, 15 fathers) of 24 TGNC children ages 4–11 years old. Parents of TGNC children described how 4 prespecified domains of emotional and behavioral problems (i.e., oppositional behavior, anger, sadness, and fears/worries) are characterized in the context of gender-nonconformity/GD. Parents also identified precipitants of these problems. Overall study findings indicate there is a role for EBI adaptation as parents identified many different examples of emotional and behavioral challenges emerging in unique and nuanced ways in TGNC children.
Psychosocial Screening for Siblings of Children With Cancer: Barriers and Preferences
Authors: Long Kristin A. , Pariseau Emily M. , Muriel Anna C. , Chu Andrea , Kazak Anne E. , Leon Michelle , Alderfer Melissa A.
Published: December 2017

Although many siblings show resilience in the face of childhood cancer, others report clinical levels of distress during and after cancer treatment. Psychosocial care is recommended for siblings, but systematic screening to identify siblings currently experiencing or at-risk for psychosocial difficulties is not routine. As part of a program of research to develop feasible procedures for sibling screening, the current study used qualitative methods to gather the perspectives of parents and siblings regarding barriers to sibling psychosocial screening, ways to mitigate those barriers, and preferred screening procedures. A purposive sample of families of children with cancer ( n = 29 parents, n = 17 siblings ages 8–17) participated in semistructured qualitative interviews. Barriers to and preferences for sibling screening (e.g., timing, location, modality) were probed. Applied thematic analysis was used to distill findings. Families reported a strong need for sibling psychosocial screening but also reported barriers (i.e., family disruptions and separations, parental stress, and hesitancy to disclose emotional difficulties by both siblings and parents). Recommendations for addressing these barriers were provided. Sibling screening was preferred near diagnosis and every three months thereafter. Parent and sibling reports were both recommended. Preferred modalities included electronic questionnaire delivered in the hospital/clinic (parents) and clinical interview (siblings). In sum, families emphasized the importance of sibling psychosocial screening and suggested ways to achieve this. Involving families in the development of procedures to systematically screen siblings of children with cancer for psychosocial difficulties is an important step in developing feasible, effective strategies to identify siblings in need of clinical care.
Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer
Authors: Ramakrishnan Swathi , Hu Qiang , Krishnan Nithya , Wang Dan , Smit Evelyn , Granger Victoria , Rak Monika , Attwood Kristopher , Johnson Candace , Morrison Carl , Pili Roberto , Chatta Gurkamal , Guru Khurshid , Gueron Geraldine , McNally Lacey , Wang Jianmin , Woloszynska-Read Anna
Published: December 2017

Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation. Importantly, DAC treatment increases ICN1 expression (the active intracellular domain of NOTCH1) significantly inhibiting cell proliferation and causing changes in cell size inducing morphological alterations reminiscent of senescence. These changes were not associated with β-galactosidase activity or increased p16 levels, but instead were associated with substantial IL-6 release. Increased IL-6 release was observed in both DAC-treated and ICN1 overexpressing cells as compared to control cells. Exogenous IL-6 expression was associated with a similar enlarged cell morphology that was rescued by the addition of a monoclonal antibody against IL-6. Treatment with DAC, overexpression with ICN1 or addition of exogenous IL-6 showed CK5 reduction, a surrogate marker of differentiation. Overall this study suggests that in MIBC cells, DNA hypomethylation increases NOTCH1 expression and IL-6 release to induce CK5-related differentiation.
Supervised learning in spiking neural networks with FORCE training
Authors: Nicola Wilten , Clopath Claudia
Published: December 2017

Populations of neurons display an extraordinary diversity in the behaviors they affect and display. Machine learning techniques have recently emerged that allow us to create networks of model neurons that display behaviors of similar complexity. Here we demonstrate the direct applicability of one such technique, the FORCE method, to spiking neural networks. We train these networks to mimic dynamical systems, classify inputs, and store discrete sequences that correspond to the notes of a song. Finally, we use FORCE training to create two biologically motivated model circuits. One is inspired by the zebra finch and successfully reproduces songbird singing. The second network is motivated by the hippocampus and is trained to store and replay a movie scene. FORCE trained networks reproduce behaviors comparable in complexity to their inspired circuits and yield information not easily obtainable with other techniques, such as behavioral responses to pharmacological manipulations and spike timing statistics.
Interdependent action of KH domain proteins Krr1 and Dim2 drive the 40S platform assembly
Authors: Sturm Miriam , Cheng Jingdong , Baßler Jochen , Beckmann Roland , Hurt Ed
Published: December 2017

Ribosome biogenesis begins in the nucleolus with the formation of 90S pre-ribosomes, from which pre-40S and pre-60S particles arise that subsequently follow separate maturation pathways. Here, we show how structurally related assembly factors, the KH domain proteins Krr1 and Dim2, participate in ribosome assembly. Initially, Dim2 (Pno1) orchestrates an early step in small subunit biogenesis through its binding to a distinct region of the 90S pre-ribosome. This involves Utp1 of the UTP-B module, and Utp14, an activator of the DEAH-box helicase Dhr1 that catalyzes the removal of U3 snoRNP from the 90S. Following this dismantling reaction, the pre-40S subunit emerges, but Dim2 relocates to the pre-40S platform domain, previously occupied in the 90S by the other KH factor Krr1 through its interaction with Rps14 and the UTP-C module. Our findings show how the structurally related Krr1 and Dim2 can control stepwise ribosome assembly during the 90S-to-pre-40S subunit transition.
Reduced biomass burning emissions reconcile conflicting estimates of the post-2006 atmospheric methane budget
Authors: Worden John R. , Bloom A. Anthony , Pandey Sudhanshu , Jiang Zhe , Worden Helen M. , Walker Thomas W. , Houweling Sander , Röckmann Thomas
Published: December 2017

Several viable but conflicting explanations have been proposed to explain the recent ~8 p.p.b. per year increase in atmospheric methane after 2006, equivalent to net emissions increase of ~25 Tg CH4 per year. A concurrent increase in atmospheric ethane implicates a fossil source; a concurrent decrease in the heavy isotope content of methane points toward a biogenic source, while other studies propose a decrease in the chemical sink (OH). Here we show that biomass burning emissions of methane decreased by 3.7 (±1.4) Tg CH4 per year from the 2001–2007 to the 2008–2014 time periods using satellite measurements of CO and CH4, nearly twice the decrease expected from prior estimates. After updating both the total and isotopic budgets for atmospheric methane with these revised biomass burning emissions (and assuming no change to the chemical sink), we find that fossil fuels contribute between 12–19 Tg CH4 per year to the recent atmospheric methane increase, thus reconciling the isotopic- and ethane-based results.
NAIP/NLRC4 inflammasome activation in MRP8+ cells is sufficient to cause systemic inflammatory disease
Authors: Nichols Randilea D. , von Moltke Jakob , Vance Russell E.
Published: December 2017

Inflammasomes are cytosolic multiprotein complexes that initiate protective immunity in response to infection, and can also drive auto-inflammatory diseases, but the cell types and signalling pathways that cause these diseases remain poorly understood. Inflammasomes are broadly expressed in haematopoietic and non-haematopoietic cells and can trigger numerous downstream responses including production of IL-1β, IL-18, eicosanoids and pyroptotic cell death. Here we show a mouse model with endogenous NLRC4 inflammasome activation in Lysozyme2+ cells (monocytes, macrophages and neutrophils) in vivo exhibits a severe systemic inflammatory disease, reminiscent of human patients that carry mutant auto-active NLRC4 alleles. Interestingly, specific NLRC4 activation in Mrp8+ cells (primarily neutrophil lineage) is sufficient to cause severe inflammatory disease. Disease is ameliorated on an Asc−/− background, and can be suppressed by injections of anti-IL-1 receptor antibody. Our results provide insight into the mechanisms by which NLRC4 inflammasome activation mediates auto-inflammatory disease in vivo.
Transient two-dimensional vibrational spectroscopy of an operating molecular machine
Authors: Panman Matthijs R. , van Dijk Chris N. , Huerta-Viga Adriana , Sanders Hans J. , Bakker Bert H. , Leigh David A. , Brouwer Albert M. , Buma Wybren Jan , Woutersen Sander
Published: December 2017

Synthetic molecular machines are promising building blocks for future nanoscopic devices. However, the details of their mechanical behaviour are in many cases still largely unknown. A deeper understanding of mechanics at the molecular level is essential for the design and construction of complex nanodevices. Here, we show that transient two-dimensional infrared (T2DIR) spectroscopy makes it possible to monitor the conformational changes of a translational molecular machine during its operation. Translation of a macrocyclic ring from one station to another on a molecular thread is initiated by a UV pulse. The arrival of the shuttling macrocycle at the final station is visible from a newly appearing cross peak between these two moieties. To eliminate spectral congestion in the T2DIR spectra, we use a subtraction method applicable to many other complex molecular systems. The T2DIR spectra indicate that the macrocycle adopts a boat-like conformation at the final station, which contrasts with the chair-like conformation at the initial station.
PCH1 and PCHL promote photomorphogenesis in plants by controlling phytochrome B dark reversion
Authors: Enderle Beatrix , Sheerin David J. , Paik Inyup , Kathare Praveen Kumar , Schwenk Philipp , Klose Cornelia , Ulbrich Maximilian H. , Huq Enamul , Hiltbrunner Andreas
Published: December 2017

Phytochrome B (phyB) is the primary red light photoreceptor in plants, and regulates both growth and development. The relative levels of phyB in the active state are determined by the light conditions, such as direct sunlight or shade, but are also affected by light-independent dark reversion. Dark reversion is a temperature-dependent thermal relaxation process, by which phyB reverts from the active to the inactive state. Here, we show that the homologous phyB-binding proteins PCH1 and PCHL suppress phyB dark reversion, resulting in plants with dramatically enhanced light sensitivity. Moreover, far-red and blue light upregulate the expression of PCH1 and PCHL in a phyB independent manner, thereby increasing the response to red light perceived by phyB. PCH1 and PCHL therefore provide a node for the molecular integration of different light qualities by regulation of phyB dark reversion, allowing plants to adapt growth and development to the ambient environment.
Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Authors: Hoffman Gabriel E. , Hartley Brigham J. , Flaherty Erin , Ladran Ian , Gochman Peter , Ruderfer Douglas M. , Stahl Eli A. , Rapoport Judith , Sklar Pamela , Brennand Kristen J.
Published: December 2017

The power of human induced pluripotent stem cell (hiPSC)-based studies to resolve the smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. We identified and accounted for a variety of technical and biological sources of variation in a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal and increased the concordance with post-mortem data sets. We predict a growing convergence between hiPSC and post-mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones.
Impact of grain boundaries on efficiency and stability of organic-inorganic trihalide perovskites
Authors: Chu Zhaodong , Yang Mengjin , Schulz Philip , Wu Di , Ma Xin , Seifert Edward , Sun Liuyang , Li Xiaoqin , Zhu Kai , Lai Keji
Published: December 2017

Organic–inorganic perovskite solar cells have attracted tremendous attention because of their remarkably high power conversion efficiencies. To further improve device performance, it is imperative to obtain fundamental understandings on the photo-response and long-term stability down to the microscopic level. Here, we report the quantitative nanoscale photoconductivity imaging on two methylammonium lead triiodide thin films with different efficiencies by light-stimulated microwave impedance microscopy. The microwave signals are largely uniform across grains and grain boundaries, suggesting that microstructures do not lead to strong spatial variations of the intrinsic photo-response. In contrast, the measured photoconductivity and lifetime are strongly affected by bulk properties such as the sample crystallinity. As visualized by the spatial evolution of local photoconductivity, the degradation process begins with the disintegration of grains rather than nucleation and propagation from visible boundaries between grains. Our findings provide insights to improve the electro-optical properties of perovskite thin films towards large-scale commercialization.
Contributions of changes in climatology and perturbation and the resulting nonlinearity to regional climate change
Authors: Adachi Sachiho A. , Nishizawa Seiya , Yoshida Ryuji , Yamaura Tsuyoshi , Ando Kazuto , Yashiro Hisashi , Kajikawa Yoshiyuki , Tomita Hirofumi
Published: December 2017

Future changes in large-scale climatology and perturbation may have different impacts on regional climate change. It is important to understand the impacts of climatology and perturbation in terms of both thermodynamic and dynamic changes. Although many studies have investigated the influence of climatology changes on regional climate, the significance of perturbation changes is still debated. The nonlinear effect of these two changes is also unknown. We propose a systematic procedure that extracts the influences of three factors: changes in climatology, changes in perturbation and the resulting nonlinear effect. We then demonstrate the usefulness of the procedure, applying it to future changes in precipitation. All three factors have the same degree of influence, especially for extreme rainfall events. Thus, regional climate assessments should consider not only the climatology change but also the perturbation change and their nonlinearity. This procedure can advance interpretations of future regional climates.
The HIV co-receptor CCR5 regulates osteoclast function
Authors: Lee Ji-Won , Hoshino Akiyoshi , Inoue Kazuki , Saitou Takashi , Uehara Shunsuke , Kobayashi Yasuhiro , Ueha Satoshi , Matsushima Kouji , Yamaguchi Akira , Imai Yuuki , Iimura Tadahiro
Published: December 2017

C–C chemokine receptor 5 (CCR5) is a co-receptor of HIV. Epidemiological findings suggest that the functional loss of CCR5 is correlated with a lower incidence of bone-destructive diseases as well as of HIV transmission. However, it is not clear whether CCR5 is involved in regulation of the function of bone cells, in addition to that of immune cells. Here we show that blockade of CCR5 using specific antibodies impairs human osteoclast function in vitro. Ccr5-deficient (Ccr5
−/−
) mice presented with dysfunctional osteoclasts and were resistant to osteoporosis induced by receptor activator of nuclear factor kappa-B ligand (RANKL), which triggers osteoporosis independently of inflammatory and immunomodulatory pathways. Furthermore, Ccr5 deficiency impairs the cellular locomotion and bone-resorption activity of osteoclasts, which is associated with the disarrangement of podosomes and adhesion complex molecules including Pyk2. Overall, the data provides evidence that CCR5 has an essential role in bone-destructive conditions through the functional regulation of osteoclasts.
A two-dimensional ON/OFF switching device based on anisotropic interactions of atomic quantum dots on Si(100):H
Authors: Yengui Mayssa , Duverger Eric , Sonnet Philippe , Riedel Damien
Published: December 2017

Controlling the properties of quantum dots at the atomic scale, such as dangling bonds, is a general motivation as they allow studying various nanoscale processes including atomic switches, charge storage, or low binding energy state interactions. Adjusting the coupling of individual silicon dangling bonds to form a 2D device having a defined function remains a challenge. Here, we exploit the anisotropic interactions between silicon dangling bonds on n-type doped Si(100):H surface to tune their hybridization. This process arises from interactions between the subsurface silicon network and dangling bonds inducing a combination of Jahn–Teller distortions and local charge ordering. A three-pointed star-shaped device prototype is designed. By changing the charge state of this device, its electronic properties are shown to switch reversibly from an ON to an OFF state via local change of its central gap. Our results provide a playground for the study of quantum information at the nanoscale.
Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis
Authors: Lee Ji-Eun , Park Young-Kwon , Park Sarah , Jang Younghoon , Waring Nicholas , Dey Anup , Ozato Keiko , Lai Binbin , Peng Weiqun , Ge Kai
Published: December 2017

The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and CBP/p300-mediated H3K27ac, on enhancers. Consequently, Brd4 deletion prevents enhancer RNA production, cell identity gene induction and cell differentiation. Interestingly, Brd4 is dispensable for maintaining cell identity genes in differentiated cells. These findings identify Brd4 as an enhancer epigenomic reader that links active enhancers with cell identity gene induction in differentiation.
Electromigration Mechanism of Failure in Flip-Chip Solder Joints Based on Discrete Void Formation
Authors: Chang Yuan-Wei , Cheng Yin , Helfen Lukas , Xu Feng , Tian Tian , Scheel Mario , Di Michiel Marco , Chen Chih , Tu King-Ning , Baumbach Tilo
Published: December 2017

In this investigation, SnAgCu and SN100C solders were electromigration (EM) tested, and the 3D laminography imaging technique was employed forin-situobservation of the microstructure evolution during testing. We found that discrete voids nucleate, grow and coalesce along the intermetallic compound/solder interface during EM testing. A systematic analysis yields quantitative information on the number, volume, and growth rate of voids, and the EM parameter of DZ*. We observe that fast intrinsic diffusion in SnAgCu solder causes void growth and coalescence, while in the SN100C solder this coalescence was not significant. To deduce the current density distribution, finite-element models were constructed on the basis of the laminography images. The discrete voids do not change the global current density distribution, but they induce the local current crowding around the voids: this local current crowding enhances the lateral void growth and coalescence. The correlation between the current density and the probability of void formation indicates that a threshold current density exists for the activation of void formation. There is a significant increase in the probability of void formation when the current density exceeds half of the maximum value.
The importance of filamentous cyanobacteria in the development of oxygenic photogranules
Authors: Milferstedt Kim , Kuo-Dahab W. Camilla , Butler Caitlyn S. , Hamelin Jérôme , Abouhend Ahmed S. , Stauch-White Kristie , McNair Adam , Watt Christopher , Carbajal-González Blanca I. , Dolan Sona , Park Chul
Published: December 2017

Microorganisms often respond to their environment by growing as densely packed communities in biofilms, flocs or granules. One major advantage of life in these aggregates is the retention of its community in an ecosystem despite flowing water. We describe here a novel type of granule dominated by filamentous and motile cyanobacteria of the order Oscillatoriales. These bacteria form a mat-like photoactive outer layer around an otherwise unconsolidated core. The spatial organization of the phototrophic layer resembles microbial mats growing on sediments but is spherical. We describe the production of these oxygenic photogranules under static batch conditions, as well as in turbulently mixed bioreactors. Photogranulation defies typically postulated requirements for granulation in biotechnology, i.e., the need for hydrodynamic shear and selective washout. Photogranulation as described here is a robust phenomenon with respect to inoculum characteristics and environmental parameters like carbon sources. A bioprocess using oxygenic photogranules is an attractive candidate for energy-positive wastewater treatment as it biologically couples CO2 and O2 fluxes. As a result, the external supply of oxygen may become obsolete and otherwise released CO2 is fixed by photosynthesis for the production of an organic-rich biofeedstock as a renewable energy source.
Structural connections in the brain in relation to gender identity and sexual orientation
Authors: Burke Sarah M. , Manzouri Amir H. , Savic Ivanka
Published: December 2017

Both transgenderism and homosexuality are facets of human biology, believed to derive from different sexual differentiation of the brain. The two phenomena are, however, fundamentally unalike, despite an increased prevalence of homosexuality among transgender populations. Transgenderism is associated with strong feelings of incongruence between one’s physical sex and experienced gender, not reported in homosexual persons. The present study searches to find neural correlates for the respective conditions, using fractional anisotropy (FA) as a measure of white matter connections that has consistently shown sex differences. We compared FA in 40 transgender men (female birth-assigned sex) and 27 transgender women (male birth-assigned sex), with both homosexual (29 male, 30 female) and heterosexual (40 male, 40 female) cisgender controls. Previously reported sex differences in FA were reproduced in cis-heterosexual groups, but were not found among the cis-homosexual groups. After controlling for sexual orientation, the transgender groups showed sex-typical FA-values. The only exception was the right inferior fronto-occipital tract, connecting parietal and frontal brain areas that mediate own body perception. Our findings suggest that the neuroanatomical signature of transgenderism is related to brain areas processing the perception of self and body ownership, whereas homosexuality seems to be associated with less cerebral sexual differentiation.
Structure and function of the microbial consortia of activated sludge in typical municipal wastewater treatment plants in winter
Authors: Zhang Bo , Xu Xiangyang , Zhu Liang
Published: December 2017

To better understand the relationship between the environmental variables and microbial communities of activated sludge, we took winter samples from different biological treatment units (anaerobic, oxic, etc) from the WWTP’s of a number of Chinese cities. Differences in influent organic components and activated sludge microbial communities were identified by gas chromatography-mass spectrometry and high-throughput sequencing technology, respectively. Liquid nitrogen grinding pretreatment of samples was found to aid in the obtaining of a more bio-diversified sample. Influent type and dissolved oxygen concentration influenced the activated sludge microbial community structure. Nitrospira, Caldilineaceae and Anaerolineaceae were highly related to domestic wastewater treatment systems, whereas Thauera was the most abundant putative refractory aromatic hydrocarbon decomposer found in industrial wastewater treatment systems. Within the influent composition, we speculate that Thauera, Macellibacteroides and Desulfomicrobium are the key functional genera of the anaerobic environment of the textile dyeing industry wastewater treatment systems, whilst Thauera and Thiobacillus are key functional microbes in fine chemical wastewater treatment systems.
Subtalar Joint Pronation and Energy Absorption Requirements During Walking are Related to Tibialis Posterior Tendinous Tissue Strain
Authors: Maharaj Jayishni N. , Cresswell Andrew G. , Lichtwark Glen A.
Published: December 2017

During human walking, the tibialis posterior (TP) tendon absorbs energy in early stance as the subtalar joint (STJ) pronates. However, it remains unclear whether an increase in energy absorption between individuals, possibly a result of larger STJ pronation displacement, is fulfilled by greater magnitudes of TP tendon or muscle fascicle strain. By collecting direct measurements of muscle fascicle length (ultrasound), MTU length (3D motion capture and musculoskeletal modelling), and TP muscle activation (intramuscular electromyography) we endeavoured to illustrate that the TP tendinous tissue fulfils the requirements for energy absorption at the STJ as a result of an increase in muscle force production. While a significant relationship between TP tendon strain, energy absorption at the STJ (R2 = 0.53, P = < 0.01) and STJ pronation (R2 = 0.53, P = < 0.01) was evident, we failed to find any significant associations between tendon strain and surrogate measure of TP muscle force (TP muscle activation together with ankle and subtalar joint moments). These results suggest that TP tendon compliance may explain the variance in pronation and energy absorption at the STJ. Therefore, as the tendinous tissue of the TP is accountable for the absorption of energy at the STJ it may be predisposed to strain-induced injury.
Machine Learning for Nuclear Mechano-Morphometric Biomarkers in Cancer Diagnosis
Authors: Radhakrishnan Adityanarayanan , Damodaran Karthik , Soylemezoglu Ali C. , Uhler Caroline , Shivashankar G. V.
Published: December 2017

Current cancer diagnosis employs various nuclear morphometric measures. While these have allowed accurate late-stage prognosis, early diagnosis is still a major challenge. Recent evidence highlights the importance of alterations in mechanical properties of single cells and their nuclei as critical drivers for the onset of cancer. We here present a method to detect subtle changes in nuclear morphometrics at single-cell resolution by combining fluorescence imaging and deep learning. This assay includes a convolutional neural net pipeline and allows us to discriminate between normal and human breast cancer cell lines (fibrocystic and metastatic states) as well as normal and cancer cells in tissue slices with high accuracy. Further, we establish the sensitivity of our pipeline by detecting subtle alterations in normal cells when subjected to small mechano-chemical perturbations that mimic tumor microenvironments. In addition, our assay provides interpretable features that could aid pathological inspections. This pipeline opens new avenues for early disease diagnostics and drug discovery.
Inhaled bronchodilators and acute myocardial infarction: a nested case-control study
Authors: Lee Chang-Hoon , Choi Seongmi , Jang Eun Jin , Yang Han-Mo , Il Yoon Ho , Kim Yun Jung , Kim Jimin , Yim Jae-Joon , Kim Deog Kyeom
Published: December 2017

We investigated the association between the use of inhaled bronchodilators and the risk of AMI. A nested case-control study using the nationwide insurance claims database was conducted. Overall, 11,054 AMI cases and 47,815 matched (up to 1:5) controls were identified from 1,036,119 subjects without acute major cardiovascular events in the past year. Long-acting and short-acting β-agonists (LABAs and SABAs) were associated with increase in the risk of AMI, although an inhaled corticosteroid combined with a long-acting β-agonist was not. Long-acting muscarinic antagonists (LAMAs) in a dry powder inhaler (DPI) were significantly associated with reduced risk of AMI, while LAMAs in a soft mist inhaler (SMI) didn’t decrease the risk of it. In hypertensive or diabetic patients, LAMAs in a DPI were associated with reduced risk of AMI, but LABAs were associated with increased risk. Among the β-blocker users, the reduction of AMI risk by LAMAs was the most significant. In conclusions, inhaled β-agonists were associated with increase in the risk of AMI, while LABAs accompanied by ICSs were not associated with increase in the risk of AMI. LAMAs in a DPI use were associated with lower risk of AMI.
Enhancing security of incoherent optical cryptosystem by a simple position-multiplexing technique and ultra-broadband illumination
Authors: Sahoo Sujit Kumar , Tang Dongliang , Dang Cuong
Published: December 2017

A position-multiplexing technique with ultra-broadband illumination is proposed to enhance the information security of an incoherent optical cryptosystem. This simplified optical encryption system only contains one diffuser acting as the random phase mask (RPM). Incoherent light coming from a plaintext passes through this nature RPM and generates the corresponding ciphertext on a camera. The proposed system effectively reduces problems of critical alignment sensitivity and coherent noise that are found in the coherent illumination. Here, the use of ultra-broadband illumination has the advantage of reducing the speckle contrast that makes the ciphertext more complex. Reduction of the ciphertext size further increases the strength of the ciphering. Using the spatial decorrelation of the speckle pattern we have demonstrated a position multiplexed based cryptosystem, where the ciphertext is the superposition of uniquely encrypted texts from various spatial positions. These unique spatial keys are utilized to decrypt the plaintext located at different spatial positions, and a complete decrypted text can be concatenated with high fidelity. Benefiting from position-multiplexing, the information of interest is scrambled together by a truly random method in a smaller ciphertext. A high performance security for an optical cryptosystem has been achieved in a simple setup with a ground glass diffuser as a nature RPM, the broadband incoherent illumination and small position-multiplexed ciphertext.
p53 and cyclin G cooperate in mediating genome stability in somatic cells of Drosophila
Authors: Bayer Fabienne E. , Zimmermann Mirjam , Fischer Patrick , Gromoll Christian , Preiss Anette , Nagel Anja C.
Published: December 2017

One of the key players in genome surveillance is the tumour suppressor p53 mediating the adaptive response to a multitude of stress signals. Here we identify Cyclin G (CycG) as co-factor of p53-mediated genome stability. CycG has been shown before to be involved in double-strand break repair during meiosis. Moreover, it is also important for mediating DNA damage response in somatic tissue. Here we find it in protein complexes together with p53, and show that the two proteins interact physically in vitro and in vivo in response to ionizing irradiation. In contrast to mammals, Drosophila Cyclin G is no transcriptional target of p53. Genetic interaction data reveal that p53 activity during DNA damage response requires the presence of CycG. Morphological defects caused by overexpression of p53 are ameliorated in cycG null mutants. Moreover, using a p53 biosensor we show that p53 activity is impeded in cycG mutants. As both p53 and CycG are likewise required for DNA damage repair and longevity we propose that CycG plays a positive role in mediating p53 function in genome surveillance of Drosophila.
RON4L1 is a new member of the moving junction complex in Toxoplasma gondii
Authors: Guérin Amandine , El Hajj Hiba , Penarete-Vargas Diana , Besteiro Sébastien , Lebrun Maryse
Published: December 2017

Apicomplexa parasites, including Toxoplasma and Plasmodium species, possess a unique invasion mechanism that involves a tight apposition between the parasite and the host plasma membranes, called “moving junction” (MJ). The MJ is formed by the assembly of the microneme protein AMA1, exposed at the surface of the parasite, and the parasite rhoptry neck (RON) protein RON2, exposed at the surface of the host cell. In the host cell, RON2 is associated with three additional parasite RON proteins, RON4, RON5 and RON8. Here we describe RON4L1, an additional member of the MJ complex in Toxoplasma. RON4L1 displays some sequence similarity with RON4 and is cleaved at the C-terminal end before reaching the rhoptry neck. Upon secretion during invasion, RON4L1 is associated with MJ and targeted to the cytosolic face of the host membrane. We generated a RON4
L1
knock-out cell line and showed that it is not essential for the lytic cycle in vitro, although mutant parasites kill mice less efficiently. Similarly to RON8, RON4L1 is a coccidian-specific protein and its traffic to the MJ is not affected in absence of RON2, RON4 and RON5, suggesting the co-existence of independent MJ complexes in tachyzoite of Toxoplasma.
Heartbeat Complexity Modulation in Bipolar Disorder during Daytime and Nighttime
Authors: Nardelli Mimma , Lanata Antonio , Bertschy Gilles , Scilingo Enzo Pasquale , Valenza Gaetano
Published: December 2017

This study reports on the complexity modulation of heartbeat dynamics in patients affected by bipolar disorder. In particular, a multiscale entropy analysis was applied to the R-R interval series, that were derived from electrocardiographic (ECG) signals for a group of nineteen subjects comprised of eight patients and eleven healthy control subjects. They were monitored using a textile-based sensorized t-shirt during the day and overnight for a total of 47 diurnal and 27 nocturnal recordings. Patients showed three different mood states: depression, hypomania and euthymia. Results show a clear loss of complexity during depressive and hypomanic states as compared to euthymic and healthy control states. In addition, we observed that a more significant complexity modulation among healthy and pathological mood states occurs during the night. These findings suggest that bipolar disorder is associated with an enhanced sleep-related dysregulation of the Autonomic Nervous System (ANS) activity, and that heartbeat complex dynamics may serve as a viable marker of pathological conditions in mental health.
Stroboscopic vision and sustained attention during coincidence-anticipation
Authors: Ballester Rafael , Huertas Florentino , Uji Makoto , Bennett Simon J.
Published: December 2017

We compared coincidence-anticipation performance in normal vision and stroboscopic vision as a function of time-on-task. Participants estimated the arrival time of a real object that moved with constant acceleration (−0.7, 0, +0.7 m/s2) in a pseudo-randomised order across 4 blocks of 30 trials in both vision conditions, received in a counter-balanced order. Participants (n = 20) became more errorful (accuracy and variability) in the normal vision condition as a function of time-on-task, whereas performance was maintained in the stroboscopic vision condition. We interpret these data as showing that participants failed to maintain coincidence-anticipation performance in the normal vision condition due to monotony and attentional underload. In contrast, the stroboscopic vision condition placed a greater demand on visual-spatial memory for motion extrapolation, and thus participants did not experience the typical vigilance decrement in performance. While short-term adaptation effects from practicing in stroboscopic vision are promising, future work needs to consider for how long participants can maintain effortful processing, and whether there are negative carry-over effects from cognitive fatigue when transferring to normal vision.
Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic
Authors: Arras Samantha D. M. , Ormerod Kate L. , Erpf Paige E. , Espinosa Monica I. , Carpenter Alex C. , Blundell Ross D. , Stowasser Samantha R. , Schulz Benjamin L. , Tanurdzic Milos , Fraser James A.
Published: December 2017

Reference strains are a key component of laboratory research, providing a common background allowing for comparisons across a community of researchers. However, laboratory passage of these strains has been shown to lead to reduced fitness and the attenuation of virulence in some species. In this study we show the opposite in the fungal pathogen Cryptococcus neoformans, with analysis of a collection of type strain H99 subcultures revealing that the most commonly used laboratory subcultures belong to a mutant lineage of the type strain that is hypervirulent. The pleiotropic mutant phenotypes in this H99L (for “Laboratory”) lineage are the result of a deletion in the gene encoding the SAGA Associated Factor Sgf29, a mutation that is also present in the widely-used H99L-derived KN99a/α congenic pair. At a molecular level, loss of this gene results in a reduction in histone H3K9 acetylation. Remarkably, analysis of clinical isolates identified loss of function SGF29 mutations in C. neoformans strains infecting two of fourteen patients, demonstrating not only the first example of hypervirulence in clinical C. neoformans samples, but also parallels between in vitro and in vivo microevolution for hypervirulence in this important pathogen.
Atomic structural details of a protein grafted onto gold nanoparticles
Authors: Giuntini Stefano , Cerofolini Linda , Ravera Enrico , Fragai Marco , Luchinat Claudio
Published: December 2017

The development of a methodology for the structural characterization at atomic detail of proteins conjugated to nanoparticles would be a breakthrough in nanotechnology. Solution and solid-state NMR spectroscopies are currently used to investigate molecules and peptides grafted onto nanoparticles, but the strategies used so far fall short in the application to proteins, which represent a thrilling development in theranostics. We here demonstrate the feasibility of highly-resolved multidimensional heteronuclear spectra of a large protein assembly conjugated to PEGylated gold nanoparticles. The spectra have been obtained by direct proton detection under fast MAS and allow for both a fast fingerprinting for the assessment of the preservation of the native fold and for resonance assignment. We thus demonstrate that the structural characterization and the application of the structure-based methodologies to proteins bound to gold nanoparticles is feasible and potentially extensible to other hybrid protein-nanomaterials.
Single-cell-based evaluation of sperm progressive motility via fluorescent assessment of mitochondria membrane potential
Authors: Moscatelli Natalina , Spagnolo Barbara , Pisanello Marco , Lemma Enrico Domenico , De Vittorio Massimo , Zara Vincenzo , Pisanello Ferruccio , Ferramosca Alessandra
Published: December 2017

Sperm cells progressive motility is the most important parameter involved in the fertilization process. Sperm middle piece contains mitochondria, which play a critical role in energy production and whose proper operation ensures the reproductive success. Notably, sperm progressive motility is strictly related to mitochondrial membrane potential (MMP) and consequently to mitochondrial functionality. Although previous studies presented an evaluation of mitochondrial function through MMP assessment in entire sperm cells samples, a quantitative approach at single-cell level could provide more insights in the analysis of semen quality. Here we combine laser scanning confocal microscopy and functional fluorescent staining of mitochondrial membrane to assess MMP distribution among isolated spermatozoa. We found that the sperm fluorescence value increases as a function of growing progressive motility and that such fluorescence is influenced by MMP disruptors, potentially allowing for the discrimination of different quality classes of sperm cells in heterogeneous populations.
Chemical and physical factors of desensitizing and/or anti-erosive toothpastes associated with lower erosive tooth wear
Authors: João-Souza Samira Helena , Lussi Adrian , Baumann Tommy , Scaramucci Taís , Aranha Ana Cecília Corrêa , Carvalho Thiago Saads
Published: December 2017

Toothpastes have a complex formulation and their different chemical and physical factors will influence their effectiveness against erosive tooth wear (ETW). We, therefore, investigated the effect of different desensitizing and/or anti-erosive toothpastes on initial enamel erosion and abrasion, and analysed how the interplay of their chemical and physical factors influences ETW. Human enamel specimens were submitted to 5 erosion-abrasion cycles using 9 different toothpastes and an artificial saliva group, and enamel surface loss (SL) was calculated. Chemical and physical factors (pH; presence of tin; calcium, phosphate and fluoride concentrations; % weight of solid particles; wettability; and particle size) of the toothpaste slurries were then analysed and associated with the amount of SL in a multivariate model. We observed that all desensitizing and/or anti-erosive toothpastes presented different degrees of SL. Besides pH and fluoride, all other chemical and physical factors were associated with SL. The results of this experiment indicate that enamel SL occurs independent of whether the toothpastes have a desensitizing or anti-erosive claim, and that lower SL is associated with the presence of tin, higher concentration of calcium and phosphate, higher % weight of solid particles, smaller particle size, and lower wettability.
Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84
Authors: Mahmud Zobaer Al , Jenkins Laura , Ulven Trond , Labéguère Frédéric , Gosmini Romain , De Vos Steve , Hudson Brian D. , Tikhonova Irina G. , Milligan Graeme
Published: December 2017

Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3′-diindolylmethane. 3,3′-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3′-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine172, located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3′-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3′-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [3H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3′-diindolylmethane and was not affected adversely by mutation of arginine172. These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings.