bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMalaria 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

AbstractNuclear 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

AbstractBanana 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

AbstractThe 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

AbstractThe 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

AbstractKoala 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

AbstractAllostery, 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

AbstractWe 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

AbstractEfficient 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

AbstractRecent 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

AbstractSecreted 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

AbstractTechnologies 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

AbstractStore-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

AbstractSOCS2 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.
A Strategic Design of an Opto-Chemical Security Device with Resettable and Reconfigurable Password Based Upon Dual Channel Two-in-One Chemosensor Molecule
Authors: Majumdar Tapas , Haldar Basudeb , Mallick Arabinda 
Published: February 2017

AbstractA simple strategy is proposed to design and develop an intelligent device based on dual channel ion responsive spectral properties of a commercially available molecule, harmine (HM). The system can process different sets of opto-chemical inputs generating different patterns as fluorescence outputs at specific wavelengths which can provide an additional level of protection exploiting both password and pattern recognitions. The proposed system could have the potential to come up with highly secured combinatorial locks at the molecular level that could pose valuable real time and on-site applications for user authentication.