bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete genome characterization and evolutionary analysis of serotype-4 associated with severe dengue
Authors: VADDADI K. , GANDIKOTA C. , VENKATARAMANA M.
Published: February 2017

Dengue virus circulates as four independent serotypes posing a major public health threat around the globe. In the recent years, frequent dengue outbreaks are being reported in many parts of the world including India. Among four serotypes, Den-4 is the least sampled and studied serotype until recent times, but the reported cases with Den-4 infections were mostly known to associate with severe dengue. In the past three decades, only one complete genome sequence of Den-4 has been published from India. Hence there is a deficit in information with reference to this serotype which would be required in deciphering its association with severe dengue. In this study, we have carried out the complete genome characterization of Den-4 virus, isolated from a dengue shock syndrome patient during the 2015 outbreak from Hyderabad, South India. Phylogenetic analysis revealed the circulation of genotype I (lineage C) which showed close relatedness to the reported virulent strains. The data also indicated few unique amino acid substitutions which are known to be important in virus replication and epitope presentation. This is the first report of complete genome characterization of Den-4 from South India, which may assist in shaping the genetic diversity of circulating strains in India.
Social experience and psychosis. Insights from studies of migrant and ethnic minority groups
Authors: Morgan Craig , Fearon Paul
Published: February 2017

In this paper we aim to provide an overview of initial findings from the UK ÆSOP study concerning ethnicity, social risk factors and psychosis, and to set the findings from this study within the context of other related research. Our focus is primarily on the UK African-Caribbean population. ÆSOP is a multi-centre population based incidence and case-control study of first episode psychosis, conducted initially over a three-year period. The study sample comprises: a) all patients with a first episode of psychosis who presented to secondary and tertiary services within tightly defined catchment areas in south-east London, Nottingham and Bristol, UK over defined time periods; and b) a random sample of healthy community controls. Findings from the ÆSOP study to date have confirmed that the African-Caribbean and Black African populations in the UK are at increased risk of schizophrenia and other psychoses, compared with the White British population. Analyses of data relating to social risk factors suggest that various forms of early childhood and adult adversity, and neighbourhood characteristics, including ethnic density, may be particularly important in contributing to increased risk in these populations. These data suggest that adverse social experiences maybe aetiologically relevant in schizophrenia and other psychoses. A more complete understanding of these factors may help us to clarify why there are differences in rates between populations.
The long and winding journey of Outsider Art. An historical perspective
Authors: Tansella Carole
Published: February 2017

Aims - The article describes the evolution of Outsider Art from the birth of its term in 1972 to the present and its emancipation from the margin to the markets, still in progress. Results - Tracing the evolution of Outsider Art evidences a stark contradiction. On one hand the art world of collectors, historians, art dealers and admirateurs, accepts without reservation artwork that for many years was kept in a marginal position, compared to the “insider” art establishment. On the other hand art experts can not agree on a universal definition of this category of art. The particular status of the outsider artists is one of the reasons that causes difficulty in reaching a definition of Outsider Art. Significant atelier experiences with psychiatric patients delineate the difference between an Outsider Art work and a work produced by Art Therapy. Conclusions - The art market of art dealers and art collectors can be identified as the place where these contradictions dissolve, and where the Outsider Art category finds its ultimate legitimation and international recognition.
Clinical vs. structured interview on anxiety and affective disorders by primary care physicians. Understanding diagnostic discordance
Authors: Balestrieri Matteo , Baldacci Sandra , Bellomo Antonello , Bellantuono Cesario , Conti Luciano , Perugi Giulio , Nardini Marcello , Borbotti Marco , Viegi Giovanni
Published: February 2017

Aims— To assess in a national sample the ability of GPs to detect psychiatric disorders using a clinical vs. a standardized interview and to characterize the patients that were falsely diagnosed with an anxiety or affective disorder.Methods— This is a national, cross—sectional, epidemiological survey, carried out by GPs on a random sample of their patients. The GPs were randomly divided into two groups. Apart from the routine clinical interview, the experimental group (group A) had to administer the Mini—International Neuropsychiatric Interview (MINI).Results— Data was collected by 143 GPs. 17.2% of all patients had a clinical diagnosis of an affective disorder, and 25.4% a clinical diagnosis of an anxiety disorder. In group A, the number of clinical diagnoses was about twice that of MINI diagnoses for affective disorders and one and a half times that for anxiety disorders. The majority of clinical diagnoses were represented by MINI subsyndromal cases (52.3%). Females showed a higher OR of being over—detected by GPs with anxiety disorders or of not being diagnosed with an affective disorder. Being divorced/separated/widowed increased the OR of over—detection of affective and anxiety disorders. The OR of over—detection of an affective or an anxiety disorder was higher for individuals with a moderate to poor quality of life.Conclusions— In the primary care a gap exists between clinical and standardized interviews in the detection of affective and anxiety disorders. Some experiential and social factors can increase this tendency. The use of a psycho.

Declaration of Interest: GlaxoSmithKline provided unrestricted economic and organizational support to the study. No further declarations on other form of financing or any other involvement that might be considered a conflict of interest in connection with the submitted article.
Beliefs about psychosocial consequences of schizophrenia and depression: a comparative study in a sample of secondary school students
Authors: Castiello Giuseppina , Magliano Lorenza
Published: February 2017

Aims — Description of students' opinions about schizophrenia and depression. Methods — The study was carried out on a sample of 445 secondary school students, randomly allocated to a “schizophrenia” or a “depression” group (N=221 and N=224, respectively). Each respondent was asked to read a case—vignette describing a case of schizophrenia or depression, and then to fill the Questionnaire on the Opinions about Mental Illness — General Population's version (QO—GP). Results — 35% of students in “schizophrenia” group vs. 85% in “depression” group attributed a correct diagnosis to case—vignette. 19% of students in the “schizophrenia” group vs. 39% in the “depression” group believed that these mental disorders can recover. Affective and civil rights were more frequently acknowledged to patients with depression than to those with schizophrenia. In both groups, the majority of students stated that mentally ill patients were unpredictable and socially dangerous. Students who reported TV stories on people with mentally ill were more frequently convinced on their unpredictability and social dangerousness. Conclusions — These results outline the need to: a) plan educational campaigns for students on mental disorders; b) alert media professionals on the impact that the way they present crimes committed by mentally ill patients may have on general population.

Declaration of Interest: None of the authors has had any interest or she has received any form of support, including that from drug companies and honoraria for lectures and consultancies potentially in conflict with this scientific work in the last two years. None of the authors has received any form of fee for her participation in this study.
Technological innovation, social learning and natural hazard mitigation: evidence on earthquake fatalities
Authors: Miao Qing
Published: February 2017

How do people learn from disasters? Do they constantly develop and accumulate new knowledge that enables them to address recurrent disaster risks? This paper investigates whether social learning and, in particular, the development of earthquake-mitigating technologies reduces earthquake-induced fatalities. Combining patent data with a global cross-section of 894 earthquakes that occurred between 1980 and 2010, we find that countries with more disaster-mitigating innovations and more earthquake exposure in the past suffer fewer fatalities. This study is the first to empirically examine the role of technological change and social learning in disaster mitigation. It sheds light on knowledge as a key element of adaptive capacity, and suggests the importance of incorporating technology development into a long-term hazard mitigation and adaptation policy. The paper also contributes to the empirical disaster literature as the first to address the problem of missing data on disaster losses.
Changes in ultrasound measures of muscle and its genetic variation during lactation in dairy cows
Authors: Sloniewski K. , Mao I. L. , Jensen J. , Madsen P.
Published: February 2017

Changes in ultrasound measures of muscle area (UtM) during lactation in different breeds and parities and with different feeding levels were examined. Random regressions were fitted to repeated measures of UtM in order to study changes in variance components of UtM during lactation. Correlations between measures taken in different stages of lactation and in different parities were also calculated. The shape of UtM curves during lactation appeared to be fairly consistent for all breeds and parities. The lowest point of all curves coincided with the expected nadir of body reserves during lactation. With lower-than-normal feeding level, the drop of UtM after calving was deeper and the overall level was lower. A major proportion of the variance in UtM was found to be determined by additive genetic variation. In all three breeds studied, repeatability and heritability estimates were high and fairly consistent during lactation and between parities. The very high genetic correlations between measures taken in different periods of lactation suggested that muscle growth and recovery are controlled by the same gene complex throughout lactation.

Our results suggest that UtM, if used jointly with other body measures such as body condition score, could be a useful indicator of tissue mobilization and deposition in the lactating cow, especially during the early stage of lactation.
Brief assessment of food insecurity accurately identifies high-risk US adults
Authors: Gundersen Craig , Engelhard Emily E , Crumbaugh Amy S , Seligman Hilary K
Published: February 2017

Objective

To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture’s Core Food Security Module.

Design

We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups.

Setting

2013 Current Population Survey December Supplement, a population-based US survey.

Subjects

All survey participants from the general population and high-risk subgroups.

Results

The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures.

Conclusions

We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household ‘worried whether food would run out before we got money to buy more’ and how often ‘the food that we bought just didn’t last and we didn’t have money to get more’. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.
Human expunction
Authors: Klee Robert
Published: February 2017

Thomas Nagel in ‘The Absurd’ (Nagel 1971) mentions the future expunction of the human species as a ‘metaphor’ for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human – indeed of everything biological in a terran sense – is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.
C-reactive protein as a marker of progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus
Authors: Pleskovič Aleš , Šantl Letonja Marija , Vujkovac Andreja Cokan , Nikolajević Starčević Jovana , Gazdikova Katarina , Caprnda Martin , Gaspar Ludovit , Kruzliak Peter , Petrovič Danijel
Published: February 2017

Abstract. Background: This prospective study was designed to evaluate the effect of inflammatory markers on the presence and progression of subclinical markers of carotid atherosclerosis in a 3.8-year follow-up period in patients with type 2 diabetes mellitus (T2DM). Patients and methods: A total of 595 subjects with T2DM were enrolled. Subclinical markers of carotid atherosclerosis (carotid intima media thickness (CIMT), plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment and again after 3.8 years. Subjects with T2DM were divided into 2 groups according to the plasma high sensitive C-reactive protein (hs-CRP) levels (subjects with hs-CRP ≥ 2 mg/L and subjects with hs-CRP below 2 mg/L). Results: Subjects with T2DM and hs-CRP levels ≥ 2 mg/L had higher CIMT in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L, and higher incidence of plaques/unstable plaques in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L. Multivariate logistic regression analysis found the association between the HDL cholesterol level and presence of plaques, whereas the inflammatory marker hs-CRP was not associated with subclinical markers of progression of carotid atherosclerosis. Multiple linear regression analysis found the association between the hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up. Conclusions: We demonstrated an association between the inflammatory marker hs-CRP and either CIMT or incidence of plaques/unstable plaques at the time of recruitment in Caucasians with T2DM. Moreover, we found the association between hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up in subjects with T2DM.
Revived Climate Change Forum Focuses on Threats to Human Health
Authors: McKenna Maryn
Published: February 2017

Public health and environmental organizations brought together by former vice president Al Gore held a pared-down meeting to replace a canceled one.
Coherent control of a strongly driven silicon vacancy optical transition in diamond
Authors: Zhou Yu , Rasmita Abdullah , Li Ke , Xiong Qihua , Aharonovich Igor , Gao Wei-bo
Published: February 2017

The ability to prepare, optically read out and coherently control single quantum states is a key requirement for quantum information processing. Optically active solid-state emitters have emerged as promising candidates with their prospects for on-chip integration as quantum nodes and sources of coherent photons connecting these nodes. Under a strongly driving resonant laser field, such quantum emitters can exhibit quantum behaviour such as Autler–Townes splitting and the Mollow triplet spectrum. Here we demonstrate coherent control of a strongly driven optical transition in silicon vacancy centre in diamond. Rapid optical detection of photons enabled the observation of time-resolved coherent Rabi oscillations and the Mollow triplet spectrum. Detection with a probing transition further confirmed Autler–Townes splitting generated by a strong laser field. The coherence time of the emitted photons is comparable to its lifetime and robust under a very strong driving field, which is promising for the generation of indistinguishable photons.
Dielectric and ferroelectric sensing based on molecular recognition in Cu(1,10-phenlothroline)2SeO4·(diol) systems
Authors: Ye Heng-Yun , Liao Wei-Qiang , Zhou Qionghua , Zhang Yi , Wang Jinlan , You Yu-Meng , Wang Jin-Yun , Chen Zhong-Ning , Li Peng-Fei , Fu Da-Wei , Huang Songping D. , Xiong Ren-Gen
Published: February 2017

The process of molecular recognition is the assembly of two or more molecules through weak interactions. Information in the process of molecular recognition can be transmitted to us via physical signals, which may find applications in sensing and switching. The conventional signals are mainly limited to light signal. Here, we describe the recognition of diols with Cu(1,10-phenlothroline)2SeO4 and the transduction of discrete recognition events into dielectric and/or ferroelectric signals. We observe that systems of Cu(1,10-phenlothroline)2SeO4·(diol) exhibit significant dielectric and/or ferroelectric dependence on different diol molecules. The compounds including ethane-1,2-diol or propane-1,2-diol just show small temperature-dependent dielectric anomalies and no reversible polarization, while the compound including ethane-1,3-diol shows giant temperature-dependent dielectric anomalies as well as ferroelectric reversible spontaneous polarization. This finding shows that dielectricity and/or ferroelectricity has the potential to be used for signalling molecular recognition.
Use of concomitant inhaled corticosteroids: pooled data from two phase III studies of aclidinium plus formoterol in COPD
Authors: D’Urzo Anthony , Singh Dave , Garcia Gil Esther
Published: February 2017

Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease. In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators. Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease. The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use. We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies. Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.
Constructing oxide interfaces and heterostructures by atomic layer-by-layer laser molecular beam epitaxy
Authors: Lei Qingyu , Golalikhani Maryam , Davidson Bruce A. , Liu Guozhen , Schlom Darrell G. , Qiao Qiao , Zhu Yimei , Chandrasena Ravini U. , Yang Weibing , Gray Alexander X. , Arenholz Elke , Farrar Andrew K. , Tenne Dmitri A. , Hu Minhui , Guo Jiandong , Singh Rakesh K. , Xi Xiaoxing
Published: February 2017

Advancements in nanoscale engineering of oxide interfaces and heterostructures have led to discoveries of emergent phenomena and new artificial materials. Combining the strengths of reactive molecular-beam epitaxy and pulsed-laser deposition, we show here, with examples of Sr1+x
Ti1-x
O3+δ, Ruddlesden–Popper phase La
n+1Ni
n
O3n+1 (n = 4), and LaAl1+y
O3(1+0.5y)/SrTiO3 interfaces, that atomic layer-by-layer laser molecular-beam epitaxy significantly advances the state of the art in constructing oxide materials with atomic layer precision and control over stoichiometry. With atomic layer-by-layer laser molecular-beam epitaxy we have produced conducting LaAlO3/SrTiO3 interfaces at high oxygen pressures that show no evidence of oxygen vacancies, a capability not accessible by existing techniques. The carrier density of the interfacial two-dimensional electron gas thus obtained agrees quantitatively with the electronic reconstruction mechanism.
Superconducting order from disorder in 2H-TaSe
2−
x
S
x
Authors: Li Lijun , Deng Xiaoyu , Wang Zhen , Liu Yu , Abeykoon Milinda , Dooryhee Eric , Tomic Aleksandra , Huang Yanan , Warren John B. , Bozin Emil S. , Billinge Simon J. L. , Sun Yuping , Zhu Yimei , Kotliar Gabriel , Petrovic Cedomir
Published: February 2017

We report on the emergence of robust superconducting order in single crystal alloys of TaSe2−
x
S
x
(0 ≤ × ≤ 2). The critical temperature of the alloy is surprisingly higher than that of the two end compounds TaSe2 and TaS2. The evolution of superconducting critical temperature Tc(x) correlates with the full width at half maximum of the Bragg peaks and with the linear term of the high-temperature resistivity. The conductivity of the crystals near the middle of the alloy series is higher or similar than that of either one of the end members 2H-TaSe2 and/or 2H-TaS2. It is known that in these materials superconductivity is in close competition with charge density wave order. We interpret our experimental findings in a picture where disorder tilts this balance in favor of superconductivity by destroying the charge density wave order.
Generating testable hypotheses for schizophrenia and rheumatoid arthritis pathogenesis by integrating epidemiological, genomic, and protein interaction data
Authors: Malavia Tulsi A. , Chaparala Srilakshmi , Wood Joel , Chowdari Kodavali , Prasad Konasale M. , McClain Lora , Jegga Anil G. , Ganapathiraju Madhavi K. , Nimgaonkar Vishwajit L.
Published: February 2017

Patients with schizophrenia and their relatives have reduced prevalence of rheumatoid arthritis. Schizophrenia and rheumatoid arthritis genome-wide association studies also indicate negative genetic correlations, suggesting that there may be shared pathogenesis at the DNA level or downstream. A portion of the inverse prevalence could be attributed to pleiotropy, i.e., variants of a single nucleotide polymorphism that could confer differential risk for these disorders. To study the basis for such an interrelationship, we initially compared lists of single nucleotide polymorphisms with significant genetic associations (p < 1e-8) for schizophrenia or rheumatoid arthritis, evaluating patterns of linkage disequilibrium and apparent pleiotropic risk profiles. Single nucleotide polymorphisms that conferred risk for both schizophrenia and rheumatoid arthritis were localized solely to the extended HLA region. Among single nucleotide polymorphisms that conferred differential risk for schizophrenia and rheumatoid arthritis, the majority were localized toHLA-B,TNXB,NOTCH4,HLA-C,HCP5,MICB,PSORS1C1, andC6orf10; published functional data indicate that HLA-B and HLA-C have the most plausible pathogenic roles in both disorders. Interactomes of these eight genes were constructed from protein–protein interaction information using publicly available databases and novel computational predictions. The genes harboring apparently pleiotropic single nucleotide polymorphisms are closely connected to rheumatoid arthritis and schizophrenia associated genes through common interacting partners. A separate and independent analysis of the interactomes of rheumatoid arthritis and schizophrenia genes showed a significant overlap between the two interactomes and that they share several common pathways, motivating functional studies suggesting a relationship in the pathogenesis of schizophrenia/rheumatoid arthritis.
Intraluminal pressure patterns in the human colon assessed by high-resolution manometry
Authors: Chen Ji-Hong , Yu Yuanjie , Yang Zixian , Yu Wen-Zhen , Chen Wu Lan , Yu Hui , Kim Marie Jeong-Min , Huang Min , Tan Shiyun , Luo Hesheng , Chen Jianfeng , Chen Jiande D. Z. , Huizinga Jan D.
Published: February 2017

Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5–230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4–5 cm apart. Synchronized haustral pressure waves, covering 3–5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3–6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal.
Proteomic analysis of exported chaperone/co-chaperone complexes of P. falciparum reveals an array of complex protein-protein interactions
Authors: Zhang Qi , Ma Cheng , Oberli Alexander , Zinz Astrid , Engels Sonja , Przyborski Jude M.
Published: February 2017

Malaria parasites modify their human host cell, the mature erythrocyte. This modification is mediated by a large number of parasite proteins that are exported to the host cell, and is also the underlying cause for the pathology caused by malaria infection. Amongst these proteins are many Hsp40 co-chaperones, and a single Hsp70. These proteins have been implicated in several processes in the host cell, including a potential role in protein transport, however the further molecular players in this process remain obscure. To address this, we have utilized chemical cross-linking followed by mass spectrometry and immunoblotting to isolate and characterize proteins complexes containing an exported Hsp40 (PFE55), and the only known exported Hsp70 (PfHsp70x). Our data reveal that both of these proteins are contained in high molecular weight protein complexes. These complexes are found both in the infected erythrocyte, and within the parasite-derived compartment referred to as the parasitophorous vacuole. Surprisingly, our data also reveal an association of PfHsp70x with components of PTEX, a putative protein translocon within the membrane of the parasitophorous vacuole. Our results suggest that theP. falciparum- infected human erythrocyte contains numerous high molecular weight protein complexes, which may potentially be involved in host cell modification.
Multi-institutional study of nuclear KIFC1 as a biomarker of poor prognosis in African American women with triple-negative breast cancer
Authors: Ogden Angela , Garlapati Chakravarthy , Li Xiaoxian , Turaga Ravi Chakra , Oprea-Ilies Gabriela , Wright Nikita , Bhattarai Shristi , Mittal Karuna , Wetherilt Ceyda Sönmez , Krishnamurti Uma , Reid Michelle D. , Jones Mildred , Gupta Meenakshi , Osan Remus , Pattni Sonal , Riaz Ansa , Klimov Sergey , Rao Arundhati , Cantuaria Guilherme , Rida Padmashree C. G. , Aneja Ritu
Published: February 2017

Nuclear KIFC1 (nKIFC1) predicts worse outcomes in breast cancer, but its prognostic value within racially distinct triple-negative breast cancer (TNBC) patients is unknown. Thus, nKIFC1 expression was assessed by immunohistochemistry in 163 African American (AA) and 144 White TNBC tissue microarrays (TMAs) pooled from four hospitals. nKIFC1 correlated significantly with Ki67 in White TNBCs but not in AA TNBCs, suggesting that nKIFC1 is not merely a surrogate for proliferation in AA TNBCs. High nKIFC1 weighted index (WI) was associated with significantly worse overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (Hazard Ratios [HRs] = 3.5, 3.1, and 3.8, respectively; P = 0.01, 0.009, and 0.007, respectively) in multivariable Cox models in AA TNBCs but not White TNBCs. Furthermore, KIFC1 knockdown more severely impaired migration in AA TNBC cells than White TNBC cells. Collectively, these data suggest that nKIFC1 WI an independent biomarker of poor prognosis in AA TNBC patients, potentially due to the necessity of KIFC1 for migration in AA TNBC cells.
Expression and distribution of extensins and AGPs in susceptible and resistant banana cultivars in response to wounding and Fusarium oxysporum
Authors: Wu Yunli , Fan Wei , Li Xiaoquan , Chen Houbin , Takáč Tomáš , Šamajová Olga , Fabrice Musana Rwalinda , Xie Ling , Ma Juan , Šamaj Jozef , Xu Chunxiang
Published: February 2017

Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is soil-borne disease of banana (Musa spp.) causing significant economic losses. Extensins and arabinogalactan proteins (AGPs) are cell wall components important for pathogen defence. Their significance for Foc resistance in banana was not reported so far. In this study, two banana cultivars differing in Foc sensitivity were used to monitor the changes in transcript levels, abundance and distribution of extensins and AGPs after wounding and Foc inoculation. Extensins mainly appeared in the root cap and meristematic cells. AGPs recognized by JIM13, JIM8, PN16.4B4 and CCRC-M134 antibodies located in root hairs, xylem and root cap. Individual AGPs and extensins showed specific radial distribution in banana roots. At the transcript level, seven extensins and 23 AGPs were differentially expressed between two banana cultivars before and after treatments. Two extensins and five AGPs responded to the treatments at the protein level. Most extensins and AGPs were up-regulated by wounding and pathogen inoculation of intact plants but down-regulated by pathogen attack of wounded plants. Main components responsible for the resistance of banana were MaELP-2 and MaPELP-2. Our data revealed that AGPs and extensins represent dynamic cell wall components involved in wounding and Foc resistance.
New type of quantum spin Hall insulators in hydrogenated PbSn thin films
Authors: Liu Liang , Qin Hongwei , Hu Jifan
Published: February 2017

The realization of a quantum spin Hall (QSH) insulator working at high temperature is of both scientific and technical interest since it supports spin-polarized and dssipationless edge states. Based on first-principle calculations, we predicted that the two-dimensional (2D) binary compound of lead and tin (PbSn) in a buckled honeycomb framework can be tuned into a topological insulator with huge a band gap and structural stability via hydrogenation or growth on special substrates. This heavy-element-based structure is sufficiently ductile to survive the 18 ps molecular dynamics (MD) annealing to 400 K, and the band gap opened by strong spin-orbital-coupling (SOC) is as large as 0.7 eV. These characteristics indicate that hydrogenated PbSn (H-PbSn) is an excellent platform for QSH realization at high temperature.
Correlated electron-nuclear dynamics in above-threshold multiphoton ionization of asymmetric molecule
Authors: Wang Zhuo , Li Min , Zhou Yueming , Lan Pengfei , Lu Peixiang
Published: February 2017

The partition of the photon energy into the subsystems of molecules determines many photon-induced chemical and physical dynamics in laser-molecule interactions. The electron-nuclear energy sharing from multiphoton ionization of molecules has been used to uncover the correlated dynamics of the electron and fragments. However, most previous studies focus on symmetric molecules. Here we study the electron-nuclear energy sharing in strong-field photoionization of HeH2+ by solving the one-dimensional time-dependent Schrödinger equation (TDSE). Compared with symmetric molecules, the joint electron-nuclear energy spectrum (JES) of HeH2+ reveals an anomalous energy shift at certain nuclear energies, while it disappears at higher and lower nuclear energies. Through tracing the time evolution of the wavepacket of bound states, we identify that this energy shift originates from the joint effect of the Stark shift, associated with the permanent dipole, and the Autler-Townes effect due to the coupling of the 2pσ and 2sσ states in strong fields. The energy shift in the JES appears at certain nuclear distances only when both Stark effect and Autler-Townes effect play important roles. We further demonstrate that the electron-nuclei energy sharing can be controlled by varying laser intensity for asymmetric molecules, providing alternative approaches to manipulate photochemical reactions for more complex molecules.
Decline causes of Koalas in South East Queensland, Australia: a 17-year retrospective study of mortality and morbidity
Authors: Gonzalez-Astudillo Viviana , Allavena Rachel , McKinnon Allan , Larkin Rebecca , Henning Joerg
Published: February 2017

Koala populations are in catastrophic decline in certain eastern Australian regions. Spanning from 1997–2013, a database derived from wildlife hospitals in southeast Queensland with N = 20,250 entries was classified by causes of morbidity and mortality. A total of 11 aetiologies were identified, with chlamydiosis, trauma, and wasting being most common. The clinical diagnosis at submission varied significantly over the observation period. Combinations of aetiologies were observed in 39% of koalas submitted, with chlamydiosis frequently co-occurring. Urogenital (cystitis 26.8%, bursitis 13.5%) and ocular (conjunctivitis 17.2%) chlamydiosis were the most frequently diagnosed representations of the infection. Approximately 26% of submissions comprised koalas involved in vehicle accidents that were otherwise healthy. Age and sex of the koala as well as season and submission period were compared for the case outcomes of ‘dead on arrival’, ‘euthanized’, or ‘released’ for the four most common clinical diagnoses using multinomial logistic regression models. Exploratory space-time permutation scans were performed and overlapping space-time clusters for chlamydiosis, motor vehicle traumas and wasting unveiled high risk areas for koala disease and injury. Our results suggest that these aetiologies are acting jointly as multifactorial determinants for the continuing decline of koalas.
A combination of mutational and computational scanning guides the design of an artificial ligand-binding controlled lipase
Authors: Kaschner Marco , Schillinger Oliver , Fettweiss Timo , Nutschel Christina , Krause Frank , Fulton Alexander , Strodel Birgit , Stadler Andreas , Jaeger Karl-Erich , Krauss Ulrich
Published: February 2017

Allostery, i.e. the control of enzyme activity by a small molecule at a location distant from the enzyme’s active site, represents a mechanism essential for sustaining life. The rational design of allostery is a non-trivial task but can be achieved by fusion of a sensory domain, which responds to environmental stimuli with a change in its structure. Hereby, the site of domain fusion is difficult to predict. We here explore the possibility to rationally engineer allostery into the naturally not allosterically regulated Bacillus subtilis lipase A, by fusion of the citrate-binding sensor-domain of the CitA sensory-kinase of Klebsiella pneumoniae. The site of domain fusion was rationally determined based on whole-protein site-saturation mutagenesis data, complemented by computational evolutionary-coupling analyses. Functional assays, combined with biochemical and biophysical studies suggest a mechanism for control, similar but distinct to the one of the parent CitA protein, with citrate acting as an indirect modulator of Triton-X100 inhibition of the fusion protein. Our study demonstrates that the introduction of ligand-dependent regulatory control by domain fusion is surprisingly facile, suggesting that the catalytic mechanism of some enzymes may be evolutionary optimized in a way that it can easily be perturbed by small conformational changes.
Large Metasurface Aperture for Millimeter Wave Computational Imaging at the Human-Scale
Authors: Gollub J. N. , Yurduseven O. , Trofatter K. P. , Arnitz D. , F. Imani M. , Sleasman T. , Boyarsky M. , Rose A. , Pedross-Engel A. , Odabasi H. , Zvolensky T. , Lipworth G. , Brady D. , Marks D. L. , Reynolds M. S. , Smith D. R.
Published: February 2017

We demonstrate a low-profile holographic imaging system at millimeter wavelengths based on an aperture composed of frequency-diverse metasurfaces. Utilizing measurements of spatially-diverse field patterns, diffraction-limited images of human-sized subjects are reconstructed. The system is driven by a single microwave source swept over a band of frequencies (17.5–26.5 GHz) and switched between a collection of transmit and receive metasurface panels. High fidelity image reconstruction requires a precise model for each field pattern generated by the aperture, as well as the manner in which the field scatters from objects in the scene. This constraint makes scaling of computational imaging systems inherently challenging for electrically large, coherent apertures. To meet the demanding requirements, we introduce computational methods and calibration approaches that enable rapid and accurate imaging performance.
Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets
Authors: Zou D. B. , Pukhov A. , Yi L. Q. , Zhuo H. B. , Yu T. P. , Yin Y. , Shao F. Q.
Published: February 2017

Efficient energy boost of the laser-accelerated ions is critical for their applications in biomedical and hadron research. Achiev-able energies continue to rise, with currently highest energies, allowing access to medical therapy energy windows. Here, a new regime of simultaneous acceleration of ~100 MeV protons and multi-100 MeV carbon-ions from plasma micro-channel targets is proposed by using a ~1020 W/cm2 modest intensity laser pulse. It is found that two trains of overdense electron bunches are dragged out from the micro-channel and effectively accelerated by the longitudinal electric-field excited in the plasma channel. With the optimized channel size, these “superponderomotive” energetic electrons can be focused on the front surface of the attached plastic substrate. The much intense sheath electric-field is formed on the rear side, leading to up to ~10-fold ionic energy increase compared to the simple planar geometry. The analytical prediction of the optimal channel size and ion maximum energies is derived, which shows good agreement with the particle-in-cell simulations.
Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome
Authors: Bulugonda Ramakrishna K. , kumar Kotha Anil , Gangappa D. , Beeda Harshavardhan , Philip Gundala Harold , Muralidhara Rao Dowlathabad , Faisal Syed M.
Published: February 2017

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.
A pan-cancer analysis of secreted Frizzled-related proteins: re-examining their proposed tumour suppressive function
Authors: Vincent Krista Marie , Postovit Lynne-Marie
Published: February 2017

Secreted frizzled-related proteins (SFRPs), containing five family members (SFRPs 1–5) are putative extracellular Wnt inhibitors. Given their abilities to inhibit Wnt signalling, as well as the loss of SFRP1 in many cancers, this family is generally considered to be tumour suppressive. In this study we analyzed gene expression, promoter methylation and survival data from over 8000 tumour and normal samples from 29 cancers in order to map the context-specific associations of SFRPs 1–5 with patient survival, gene silencing and gene expression signatures. We show that only SFRP1 associates consistently with tumour suppressive functions, and that SFRP2 and SFRP4 typically associate with a poor prognosis concomitant with the expression of genes associated with epithelial-to-mesenchymal transition. Moreover, our results indicate that while SFRP1 is lost in cancer cells via the process of DNA methylation, SFRP2 and 4 are likely derived from the tumour stroma, and thus tend to increase in tumours as compared to normal tissues. This in-depth analysis highlights the need to study each SFRP as a separate entity and suggests that SFRP2 and SFRP4 should be approached as complex matricellular proteins with functions that extend far beyond their putative Wnt antagonistic ability.
Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach
Authors: Domenyuk Valeriy , Zhong Zhenyu , Stark Adam , Xiao Nianqing , O’Neill Heather A. , Wei Xixi , Wang Jie , Tinder Teresa T. , Tonapi Sonal , Duncan Janet , Hornung Tassilo , Hunter Andrew , Miglarese Mark R. , Schorr Joachim , Halbert David D. , Quackenbush John , Poste George , Berry Donald A. , Mayer Günter , Famulok Michael , Spetzler David
Published: February 2017

Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~1011 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 106 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients.
STIM1 Phosphorylation at Y361 Recruits Orai1 to STIM1 Puncta and Induces Ca2+ Entry
Authors: Yazbeck Pascal , Tauseef Mohammad , Kruse Kevin , Amin Md-Ruhul , Sheikh Rayees , Feske Stefan , Komarova Yulia , Mehta Dolly
Published: February 2017

Store-operated Ca2+ entry (SOCE) mediates the increase in intracellular calcium (Ca2+) in endothelial cells (ECs) that regulates several EC functions including tissue-fluid homeostasis. Stromal-interaction molecule 1 (STIM1), upon sensing the depletion of (Ca2+) from the endoplasmic reticulum (ER) store, organizes as puncta that trigger store-operated Ca2+ entry (SOCE) via plasmalemmal Ca2+-selective Orai1 channels. While the STIM1 and Orai1 binding interfaces have been mapped, signaling mechanisms activating STIM1 recruitment of Orai1 and STIM1-Orai1 interaction remains enigmatic. Here, we show that ER Ca2+-store depletion rapidly induces STIM1 phosphorylation at Y361 via proline-rich kinase 2 (Pyk2) in ECs. Surprisingly, the phospho-defective STIM1-Y361F mutant formed puncta but failed to recruit Orai1, thereby preventing. SOCE Furthermore, studies in mouse lungs, expression of phosphodefective STIM1-Y361F mutant in ECs prevented the increase in vascular permeability induced by the thrombin receptor, protease activated receptor 1 (PAR1). Hence, Pyk2-dependent phosphorylation of STIM1 at Y361 is a critical phospho-switch enabling recruitment of Orai1 into STIM1 puncta leading to SOCE. Therefore, Y361 in STIM1 represents a novel target for limiting SOCE-associated vascular leak.
The ubiquitin ligase Cullin5SOCS2 regulates NDR1/STK38 stability and NF-κB transactivation
Authors: Paul Indranil , Batth Tanveer S. , Iglesias-Gato Diego , Al-Araimi Amna , Al-Haddabi Ibrahim , Alkharusi Amira , Norstedt Gunnar , Olsen Jesper V. , Zadjali Fahad , Flores-Morales Amilcar
Published: February 2017

SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative data for ~4200 proteins. Through this screen we identify a novel target of SOCS2, the serine-threonine kinase NDR1. Over-expression of SOCS2 accelerates turnover, while its knockdown stabilizes, endogenous NDR1 protein. SOCS2 interacts with NDR1 and promotes its degradation through K48-linked ubiquitination. Functionally, over-expression of SOCS2 antagonizes NDR1-induced TNFα-stimulated NF-κB activity. Conversely, depletion of NDR1 rescues the effect of SOCS2-deficiency on TNFα-induced NF-κB transactivation. Using a SOCS2−/− mice model of colitis we show that SOCS2-deficiency is pro-inflammatory and negatively correlates with NDR1 and nuclear p65 levels. Lastly, we provide evidence to suggest that NDR1 acts as an oncogene in prostate cancer. To the best of our knowledge, this is the first report of an identified E3 ligase for NDR1. These results might explain how SOCS2-deficiency leads to hyper-activation of NF-κB and downstream pathological implications and posits that SOCS2 induced degradation of NDR1 may act as a switch in restricting TNFα-NF-κB pathway.