bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability
Authors: Paul Jodi R. , DeWoskin Daniel , McMeekin Laura J. , Cowell Rita M. , Forger Daniel B. , Gamble Karen L.
Published: November 2016

How neurons encode intracellular biochemical signalling cascades into electrical signals is not fully understood. Neurons in the central circadian clock in mammals provide a model system to investigate electrical encoding of biochemical timing signals. Here, using experimental and modelling approaches, we show how the activation of glycogen synthase kinase 3 (GSK3) contributes to neuronal excitability through regulation of the persistent sodium current (INaP). INaP exhibits a day/night difference in peak magnitude and is regulated by GSK3. Using mathematical modelling, we predict and confirm that GSK3 activation of INaP affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane potential. Together, these results demonstrate a crucial link between the molecular circadian clock and electrical activity, providing examples of kinase regulation of electrical activity and the propagation of intracellular signals in neuronal networks.
Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies
Authors: Hirano Yukinori , Ihara Kunio , Masuda Tomoko , Yamamoto Takuya , Iwata Ikuko , Takahashi Aya , Awata Hiroko , Nakamura Naosuke , Takakura Mai , Suzuki Yusuke , Horiuchi Junjiro , Okuno Hiroyuki , Saitoe Minoru
Published: November 2016

Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requires the CREB transcription factor and its coactivator, CBP, subsequent early maintenance requires CREB and a different coactivator, CRTC. Late maintenance becomes CREB independent and instead requires the transcription factor Bx. Bx expression initially depends on CREB/CRTC activity, but later becomes CREB/CRTC independent. The timing of the CREB/CRTC early maintenance phase correlates with the time window for LTM extinction and we identify different subsets of CREB/CRTC target genes that are required for memory maintenance and extinction. Furthermore, we find that prolonging CREB/CRTC-dependent transcription extends the time window for LTM extinction. Our results demonstrate the dynamic nature of stored memory and its regulation by shifting transcription systems in the MBs.
Ultrafast all-optical coherent control of single silicon vacancy colour centres in diamond
Authors: Becker Jonas Nils , Görlitz Johannes , Arend Carsten , Markham Matthew , Becher Christoph
Published: November 2016

Complete control of the state of a quantum bit (qubit) is a fundamental requirement for any quantum information processing (QIP) system. In this context, all-optical control techniques offer the advantage of a well-localized and potentially ultrafast manipulation of individual qubits in multi-qubit systems. Recently, the negatively charged silicon vacancy centre (SiV−) in diamond has emerged as a novel promising system for QIP due to its superior spectral properties and advantageous electronic structure, offering an optically accessible Λ-type level system with large orbital splittings. Here, we report on all-optical resonant as well as Raman-based coherent control of a single SiV− using ultrafast pulses as short as 1 ps, significantly faster than the centre’s phonon-limited ground state coherence time of about 40 ns. These measurements prove the accessibility of a complete set of single-qubit operations relying solely on optical fields and pave the way for high-speed QIP applications using SiV− centres.
Rhodomollins A and B, two Diterpenoids with an Unprecedented Backbone from the Fruits of Rhododendron molle
Authors: Li Yong , Liu Yun-Bao , Yan Hui-Min , Liu Yang-Lan , Li Yu-Huan , Lv Hai-Ning , Ma Shuang-Gang , Qu Jing , Yu Shi-Shan
Published: November 2016

Two new grayanoids, rhodomollin A (1) and rhodomollin B (2), possessing an unprecedented D-homo grayanane carbon skeleton, were isolated from the fruits of Rhododendron molle. The structures of 1 and 2 were fully characterized using a combination of spectroscopic analyses and X-ray crystallography. Rhodomollin B (2) exhibited modest activity against influenza virus A/95-359, with an IC50 value of 19.24 μM.
Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells
Authors: Chimenti Isotta , Pagano Francesca , Cavarretta Elena , Angelini Francesco , Peruzzi Mariangela , Barretta Antonio , Greco Ernesto , De Falco Elena , Marullo Antonino G. M. , Sciarretta Sebastiano , Biondi-Zoccai Giuseppe , Frati Giacomo
Published: November 2016

Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.
Rapid Evaporative Ionisation Mass Spectrometry (REIMS) Provides Accurate Direct from Culture Species Identification within the Genus Candida
Authors: Cameron Simon J. S. , Bolt Frances , Perdones-Montero Alvaro , Rickards Tony , Hardiman Kate , Abdolrasouli Alireza , Burke Adam , Bodai Zsolt , Karancsi Tamas , Simon Daniel , Schaffer Richard , Rebec Monica , Balog Julia , Takáts Zoltan
Published: November 2016

Members of the genus Candida, such as C. albicans and C. parapsilosis, are important human pathogens. Other members of this genus, previously believed to carry minimal disease risk, are increasingly recognised as important human pathogens, particularly because of variations in susceptibilities to widely used anti-fungal agents. Thus, rapid and accurate identification of clinical Candida isolates is fundamental in ensuring timely and effective treatments are delivered. Rapid Evaporative Ionisation Mass Spectrometry (REIMS) has previously been shown to provide a high-throughput platform for the rapid and accurate identification of bacterial and fungal isolates. In comparison to commercially available matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI-ToF), REIMS based methods require no preparative steps nor time-consuming cell extractions. Here, we report on the ability of REIMS-based analysis to rapidly and accurately identify 153 clinical Candida isolates to species level. Both handheld bipolar REIMS and high-throughput REIMS platforms showed high levels of species classification accuracy, with 96% and 100% of isolates classified correctly to species level respectively. In addition, significantly different (FDR corrected P value < 0.05) lipids within the 600 to 1000 m/z mass range were identified, which could act as species-specific biomarkers in complex microbial communities.
Atomic force microscopy characterization of kinase-mediated phosphorylation of a peptide monolayer
Authors: Zhuravel Roman , Amit Einav , Elbaz Shir , Rotem Dvir , Chen Yu-Ju , Friedler Assaf , Yitzchaik Shlomo , Porath Danny
Published: November 2016

We describe the detailed microscopic changes in a peptide monolayer following kinase-mediated phosphorylation. A reversible electrochemical transformation was observed using square wave voltammetry (SWV) in the reversible cycle of peptide phosphorylation by ERK2 followed by dephosphorylation by alkaline phosphatase. A newly developed method for analyzing local roughness, measured by atomic force microscope (AFM), showed a bimodal distribution. This may indicate either a hole-formation mechanism and/or regions on the surface in which the peptide changed its conformation upon phosphorylation, resulting in increased roughness and current. Our results provide the mechanistic basis for developing biosensors for detecting kinase-mediated phosphorylation in disease.
Assessment of pathological response to therapy using lipid mass spectrometry imaging
Authors: Patterson Nathan Heath , Alabdulkarim Balqis , Lazaris Anthoula , Thomas Aurélien , Marcinkiewicz Mieczyslaw M. , Gao Zu-hua , Vermeulen Peter B. , Chaurand Pierre , Metrakos Peter
Published: November 2016

In many cancers, the establishment of a patient’s future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the ‘pathological response’ to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care.
A proteomic adaptation of small intestinal mucosa in response to dietary protein limitation
Authors: Qin Chunfu , Qiu Kai , Sun Wenjuan , Jiao Ning , Zhang Xin , Che Lianqiang , Zhao Haiyi , Shen Hexiao , Yin Jingdong
Published: November 2016

Dietary protein limitation (PL) is not only beneficial to human health but also applied to minimize nitrogen excretion in livestock production. However, the impact of PL on intestinal physiology is largely unknown. In this study, we identified 5275 quantitative proteins using a porcine model in which pigs suffered PL. A total of 202 proteins |log2 fold-change| > 1 were taken as differentially expressed proteins and subjected to functional and pathway enrichment analysis to reveal proteomic alterations of the jejunal mucosa. Combining with the results of western blotting analysis, we found that protein/carbohydrate digestion, intestinal mucosal tight junction and cell adhesion molecules, and the immune response to foreign antigens were increased in the jejunal mucosa of the pigs upon PL. In contrast, amino acid transport, innate and auto immunity, as well as cell proliferation and apoptosis were reduced. In addition, the expression of functional proteins that involved in DNA replication, transcription and mRNA splicing as well as translation were altered in the jejunal mucosa in response to PL. Furthermore, PL may reduce amino acid transport and cell proliferation through the depression of mTOR pathway. This study provides new insights into the molecular mechanisms underlying the small intestinal response to PL.
Mitsugumin 53 regulates extracellular Ca2+ entry and intracellular Ca2+ release via Orai1 and RyR1 in skeletal muscle
Authors: Ahn Mi Kyoung , Lee Keon Jin , Cai Chuanxi , Huang Mei , Cho Chung-Hyun , Ma Jianjie , Lee Eun Hui
Published: November 2016

Mitsugumin 53 (MG53) participates in the membrane repair of various cells, and skeletal muscle is the major tissue that expresses MG53. Except for the regulatory effects of MG53 on SERCA1a, the role(s) of MG53 in the unique functions of skeletal muscle such as muscle contraction have not been well examined. Here, a new MG53-interacting protein, Orai1, is identified in skeletal muscle. To examine the functional relevance of the MG53-Orai1 interaction, MG53 was over-expressed in mouse primary or C2C12 skeletal myotubes and the functional properties of the myotubes were examined using cell physiological and biochemical approaches. The PRY-SPRY region of MG53 binds to Orai1, and MG53 and Orai1 are co-localized in the plasma membrane of skeletal myotubes. MG53-Orai1 interaction enhances extracellular Ca2+entry via a store-operated Ca2+entry (SOCE) mechanism in skeletal myotubes. Interestingly, skeletal myotubes over-expressing MG53 or PRY-SPRY display a reduced intracellular Ca2+release in response to K+-membrane depolarization or caffeine stimulation, suggesting a reduction in RyR1 channel activity. Expressions of TRPC3, TRPC4, and calmodulin 1 are increased in the myotubes, and MG53 directly binds to TRPC3, which suggests a possibility that TRPC3 also participates in the enhanced extracellular Ca2+entry. Thus, MG53 could participate in regulating extracellular Ca2+entry via Orai1 during SOCE and also intracellular Ca2+release via RyR1 during skeletal muscle contraction.
Atomic insight to lattice distortions caused by carrier self-trapping in oxide materials
Authors: Freytag Felix , Corradi Gábor , Imlau Mirco
Published: November 2016

We gain hitherto missing access to the spatio-temporal evolution of lattice distortions caused by carrier self-trapping in the class of oxide materials - and beyond. The joint experimental/theoretical tool introduced combines femtosecond mid-infrared probe spectroscopy with potential landscape modeling and is based on the original approach that the vibration mode of a biatomic molecule is capable to probe strongly localized, short-lived lattice distortions in its neighborhood. Optically generated, small, strong-coupling polarons in lithium niobate, mediated by OH− ions present as ubiquitous impurities, serve as a prominent example. Polaron trapping is found to result in an experimentally determined redshift of the OH− stretching mode amounting to Δνvib = −3 cm−1, that is successfully modeled by a static Morse potential modified by Coulomb potential changes due to the displacements of the surrounding ions and the trapped charge carrier. The evolution of the trapping process can also be highlighted by monitoring the dynamics of the vibrational shift making the method an important tool for studying various systems and applications.
Glutathione-conjugating and membrane-remodeling activity of GDAP1 relies on amphipathic C-terminal domain
Authors: Huber Nina , Bieniossek Christoph , Wagner Konstanze Marion , Elsässer Hans-Peter , Suter Ueli , Berger Imre , Niemann Axel
Published: November 2016

Mutations in the ganglioside-induced differentiation associated protein 1 (GDAP1) cause severe peripheral motor and sensory neuropathies called Charcot-Marie-Tooth disease. GDAP1 expression induces fission of mitochondria and peroxisomes by a currently elusive mechanism, while disease causing mutations in GDAP1 impede the protein’s role in mitochondrial dynamics. In silico analysis reveals sequence similarities of GDAP1 to glutathione S-transferases (GSTs). However, a proof of GST activity and its possible impact on membrane dynamics are lacking to date. Using recombinant protein, we demonstrate for the first time theta-class-like GST activity for GDAP1, and it’s activity being regulated by the C-terminal hydrophobic domain 1 (HD1) of GDAP1 in an autoinhibitory manner. Moreover, we show that the HD1 amphipathic pattern is required to induce membrane dynamics by GDAP1. As both, fission and GST activities of GDAP1, are critically dependent on HD1, we propose that GDAP1 undergoes a molecular switch, turning from a pro-fission active to an auto-inhibited inactive conformation.
Quantitative fluorescence spectroscopy and flow cytometry analyses of cell-penetrating peptides internalization pathways: optimization, pitfalls, comparison with mass spectrometry quantification
Authors: Illien Françoise , Rodriguez Nicolas , Amoura Mehdi , Joliot Alain , Pallerla Manjula , Cribier Sophie , Burlina Fabienne , Sagan Sandrine
Published: November 2016

The mechanism of cell-penetrating peptides entry into cells is unclear, preventing the development of more efficient vectors for biotechnological or therapeutic purposes. Here, we developed a protocol relying on fluorometry to distinguish endocytosis from direct membrane translocation, using Penetratin, TAT and R9. The quantities of internalized CPPs measured by fluorometry in cell lysates converge with those obtained by our previously reported mass spectrometry quantification method. By contrast, flow cytometry quantification faces several limitations due to fluorescence quenching processes that depend on the cell line and occur at peptide/cell ratio >6.108 for CF-Penetratin. The analysis of cellular internalization of a doubly labeled fluorescent and biotinylated Penetratin analogue by the two independent techniques, fluorometry and mass spectrometry, gave consistent results at the quantitative and qualitative levels. Both techniques revealed the use of two alternative translocation and endocytosis pathways, whose relative efficacy depends on cell-surface sugars and peptide concentration. We confirmed that Penetratin translocates at low concentration and uses endocytosis at high μM concentrations. We further demonstrate that the hydrophobic/hydrophilic nature of the N-terminal extremity impacts on the internalization efficiency of CPPs. We expect these results and the associated protocols to help unraveling the translocation pathway to the cytosol of cells.
High and Heterogeneous Prevalence of Asymptomatic and Sub-microscopic Malaria Infections on Islands in Lake Victoria, Kenya
Authors: Idris Zulkarnain Md , Chan Chim W. , Kongere James , Gitaka Jesse , Logedi John , Omar Ahmeddin , Obonyo Charles , Machini Beatrice Kemunto , Isozumi Rie , Teramoto Isao , Kimura Masatsugu , Kaneko Akira
Published: November 2016

Kenya is intensifying its national efforts in malaria control to achieve malaria elimination. Detailed characterization of malaria infection among populations living in the areas where the disease is endemic in Kenya is a crucial priority, especially for planning and evaluating future malaria elimination strategy. This study aimed to investigate the distribution and extent of malaria infection on islands in Lake Victoria of Kenya to aid in designing new interventions for malaria elimination. Five cross-sectional surveys were conducted between January 2012 and August 2014 on four islands (Mfangano, Takawiri, Kibuogi and Ngodhe) in Lake Victoria and a coastal mainland (Ungoye). Malaria prevalence varied significantly among settings: highest in Ungoye, followed by the large island of Mfangano and lowest in the three remaining small islands. Of the 3867 malaria infections detected by PCR, 91.8% were asymptomatic, 50.3% were sub-microscopic, of which 94% were also asymptomatic. We observed geographical differences and age dependency in both proportion of sub-microscopic infections and asymptomatic parasite carriage. Our findings highlighted the local heterogeneity in malaria prevalence on islands and a coastal area in Lake Victoria, and provided support for the inclusion of mass drug administration as a component of the intervention package to eliminate malaria on islands.
Magnetic resonance imaging parameter optimizations for diagnosis of periprosthetic infection and tumor recurrence in artificial joint replacement patients
Authors: Jiang Mei-hua , He Chuan , Feng Jian-min , Li Zhi-hui , Chen Zhe , Yan Fu-hua , Lu Yong
Published: November 2016

To evaluate the efficacy of magnetic resonance imaging (MRI) parameter optimizations for the diagnosis of periprosthetic infection and tumor recurrence in joint replacement patients. We compared the quality of images for 16 joint replacement patients that were recorded using the optimized MRI parameters with and without view angle tilting (VAT) correction at 1.5 T in coronal fast-spin-echo T2-weighted MRI. The optimized MRI data of 86 patients with pain after hip replacement and 67 patients who received tumor resection and joint replacement for bone cancer were retrospectively analyzed to identify MRI features that were useful for the diagnosis of periprosthetic infection and tumor recurrence. Increasing receiver bandwidth and decreasing slice thickness combined with VAT significantly reduced the area of metal-induced artifacts. Irregular soft tissue mass, soft tissue edema, bone destruction, and fistula were significant features of periprosthetic infection, with sensitivities of 47.4–100% and specificities of 73.1–100.0%, which were confirmed based on surgical and pathological findings. Soft tissue mass was a significant feature of tumor recurrence, with 100% sensitivity, 96.0% specificity, and 97.0% consistency. The optimized VAT MRI method demonstrated a high level of diagnostic accuracy for the detection of periprosthetic infection and tumor recurrence in joint replacement patients.
3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
Authors: Giordano S. , Morosi L. , Veglianese P. , Licandro S. A. , Frapolli R. , Zucchetti M. , Cappelletti G. , Falciola L. , Pifferi V. , Visentin S. , D’Incalci M. , Davoli E.
Published: November 2016

Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.
Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer
Authors: Janakiram Naveena B. , Mohammed Altaf , Bryant Taylor , Zhang Yuting , Brewer Misty , Duff Ashley , Biddick Laura , Singh Anil , Lightfoot Stan , Steele Vernon E , Rao Chinthalapally V.
Published: November 2016

Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer.
Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder
Authors: Jiang Yali , Liu Weixiang , Ming Qingsen , Gao Yidian , Ma Ren , Zhang Xiaocui , Situ Weijun , Wang Xiang , Yao Shuqiao , Huang Bingsheng
Published: November 2016

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients.
Strong and widespread action of site-specific positive selection in the snake venom Kunitz/BPTI protein family
Authors: Župunski Vera , Kordiš Dušan
Published: November 2016

S1 family of serine peptidases is the largest family of peptidases. They are specifically inhibited by the Kunitz/BPTI inhibitors. Kunitz domain is characterized by the compact 3D structure with the most important inhibitory loops for the inhibition of S1 peptidases. In the present study we analysed the action of site-specific positive selection and its impact on the structurally and functionally important parts of the snake venom Kunitz/BPTI family of proteins. By using numerous models we demonstrated the presence of large numbers of site-specific positively selected sites that can reach between 30–50% of the Kunitz domain. The mapping of the positively selected sites on the 3D model of Kunitz/BPTI inhibitors has shown that these sites are located in the inhibitory loops 1 and 2, but also in the Kunitz scaffold. Amino acid replacements have been found exclusively on the surface, and the vast majority of replacements are causing the change of the charge. The consequence of these replacements is the change in the electrostatic potential on the surface of the Kunitz/BPTI proteins that may play an important role in the precise targeting of these inhibitors into the active site of S1 family of serine peptidases.
Effect of Schmidt number on mass transfer across a sheared gas-liquid interface in a wind-driven turbulence
Authors: Takagaki Naohisa , Kurose Ryoichi , Kimura Atsushi , Komori Satoru
Published: November 2016

The mass transfer across a sheared gas-liquid interface strongly depends on the Schmidt number. Here we investigate the relationship between mass transfer coefficient on the liquid side, kL, and Schmidt number, Sc, in the wide range of 0.7 ≤ Sc ≤ 1000. We apply a three-dimensional semi direct numerical simulation (SEMI-DNS), in which the mass transfer is solved based on an approximated deconvolution model (ADM) scheme, to wind-driven turbulence with mass transfer across a sheared wind-driven wavy gas-liquid interface. In order to capture the deforming gas-liquid interface, an arbitrary Lagrangian-Eulerian (ALE) method is employed. Our results show that similar to the case for flat gas-liquid interfaces, kL for the wind-driven wavy gas-liquid interface is generally proportional to Sc−0.5, and can be roughly estimated by the surface divergence model. This trend is endorsed by the fact that the mass transfer across the gas-liquid interface is controlled mainly by streamwise vortices on the liquid side even for the wind-driven turbulence under the conditions of low wind velocities without wave breaking.
The biosynthetic gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor contains its co-expressed vacuolar MATE transporter
Authors: Darbani Behrooz , Motawia Mohammed Saddik , Olsen Carl Erik , Nour-Eldin Hussam H. , Møller Birger Lindberg , Rook Fred
Published: November 2016

Genomic gene clusters for the biosynthesis of chemical defence compounds are increasingly identified in plant genomes. We previously reported the independent evolution of biosynthetic gene clusters for cyanogenic glucoside biosynthesis in three plant lineages. Here we report that the gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor additionally contains a gene, SbMATE2, encoding a transporter of the multidrug and toxic compound extrusion (MATE) family, which is co-expressed with the biosynthetic genes. The predicted localisation of SbMATE2 to the vacuolar membrane was demonstrated experimentally by transient expression of a SbMATE2-YFP fusion protein and confocal microscopy. Transport studies in Xenopus laevis oocytes demonstrate that SbMATE2 is able to transport dhurrin. In addition, SbMATE2 was able to transport non-endogenous cyanogenic glucosides, but not the anthocyanin cyanidin 3-O-glucoside or the glucosinolate indol-3-yl-methyl glucosinolate. The genomic co-localisation of a transporter gene with the biosynthetic genes producing the transported compound is discussed in relation to the role self-toxicity of chemical defence compounds may play in the formation of gene clusters.
Selenourea: a convenient phasing vehicle for macromolecular X-ray crystal structures
Authors: Luo Zhipu
Published: November 2016

Majority of novel X-ray crystal structures of proteins are currently solved using the anomalous diffraction signal provided by selenium after incorporation of selenomethionine instead of natural methionine by genetic engineering methods. However, selenium can be inserted into protein crystals in the form of selenourea (SeC(NH2)2), by adding the crystalline powder of selenourea into mother liquor or cryo-solution with native crystals, in analogy to the classic procedure of heavy-atom derivatization. Selenourea is able to bind to reactive groups at the surface of macromolecules primarily through hydrogen bonds, where the selenium atom may serve as acceptor and amide groups as donors. Selenourea has different chemical properties than heavy-atom reagents and halide ions and provides a convenient way of phasing crystal structures of macromolecules.
Experimental challenge of pregnant cattle with the putative abortifacient Waddlia chondrophila
Authors: Wheelhouse Nicholas , Flockhart Allen , Aitchison Kevin , Livingstone Morag , Finlayson Jeanie , Flachon Virginie , Sellal Eric , Dagleish Mark P. , Longbottom David
Published: November 2016

Waddlia chondrophila is a Gram-negative intracellular bacterial organism that is related to classical chlamydial species and has been implicated as a cause of abortion in cattle. Despite an increasing number of observational studies linking W. chondrophila infection to cattle abortion, little direct experimental evidence exists. Given this paucity of direct evidence the current study was carried out to investigate whether experimental challenge of pregnant cattle with W. chondrophila would result in infection and abortion. Nine pregnant Friesian-Holstein heifers received 2 × 108 inclusion forming units (IFU) W. chondrophila intravenously on day 105–110 of pregnancy, while four negative-control animals underwent mock challenge. Only one of the challenged animals showed pathogen-associated lesions, with the organism being detected in the diseased placenta. Importantly, the organism was re-isolated and its identity confirmed by whole genome sequencing, confirming Koch’s third and fourth postulates. However, while infection of the placenta was observed, the experimental challenge in this study did not confirm the abortifacient potential of the organism.
Inversion of inherited thrusts by wastewater injection induced seismicity at the Val d’Agri oilfield (Italy)
Authors: Buttinelli M. , Improta L. , Bagh S. , Chiarabba C.
Published: November 2016

Since 2006 wastewater has been injected below the Val d’Agri Quaternary basin, the largest on-land oilfield in Europe, inducing micro-seismicity in the proximity of a high-rate injection well. In this study, we have the rare opportunity to revise a massive set of 2D/3D seismic and deep borehole data in order to investigate the relationship between the active faults that bound the basin and the induced earthquakes. Below the injection site we identify a Pliocene thrusts and back-thrusts system inherited by the Apennines compression, with no relation with faults bounding the basin. The induced seismicity is mostly confined within the injection reservoir, and aligns coherently with a NE-dipping back-thrust favorably oriented within the current extensional stress field. Earthquakes spread upwards from the back-thrust deep portion activating a 2.5-km wide patch. Focal mechanisms show a predominant extensional kinematic testifying to an on-going inversion of the back-thrust, while a minor strike-slip compound suggests a control exerted by a high angle inherited transverse fault developed within the compressional system, possibly at the intersection between the two fault sets. We stress that where wastewater injection is active, understanding the complex interaction between injection-linked seismicity and pre-existing faults is a strong requisite for safe oilfield exploitation.
Development of functional human oral mucosal epithelial stem/progenitor cell sheets using a feeder-free and serum-free culture system for ocular surface reconstruction
Authors: Nakamura Takahiro , Yokoo Seiichi , Bentley Adams J. , Nagata Maho , Fullwood Nigel J. , Inatomi Tsutomu , Sotozono Chie , Yamagami Satoru , Kinoshita Shigeru
Published: November 2016

Ocular surface reconstruction (OSR) using tissue-engineered cultivated oral mucosal epithelial cell sheets (COMECS) is a promising newly developed treatment for patients with severe ocular surface disease. Until now, this technique has used exogenic and undefined components such as mouse-derived 3T3 feeder cells and fetal bovine serum. To minimize associated risks of zoonotic infection or transmission of unknown pathogens and so establish a safe and effective protocol for the next generation of treatment modality, we developed a novel technique for the COMECS protocol, using a feeder-free and serum-free (FFSF) culture system. Following this new protocol, COMECS exhibited 4–5 layers of well-stratified and differentiated cells, and we successfully produced functional COMECS that included holoclone-type stem cells. Immunohistochemistry confirmed the presence of markers for cell junction (ZO1, Desmoplakin), basement membrane assembly (Collagen 7, Laminin 5), differentiation (K13, K3), proliferation (Ki67) and stem/progenitor cells (p75) in the FFSF COMECS. When transplanted to the ocular surfaces of rabbits, the tissue survived for up to 2 weeks. This study represents a first step toward assessing the development of functional FFSF COMECS for safe and ideal OSR.
Rapid identification and quantification of carbohydrate excipients in Gardeniae Fructus formula granules by ATR-FTIR spectroscopy
Authors: Chen Jianbo , Sun Suqin , Zhou Qun
Published: November 2016

Formula granule is a traditional Chinese medicine (TCM) preparation usually made from the decoction of a single herbal medicinal by spray drying.
The reaction fragility spectrum
Authors: Komorowski Ludwik , Ordon Piotr , Jędrzejewski Mateusz
Published: November 2016

We report an original method that provides a new insight into the reaction mechanism by direct observation of bond breaking and formation. Example: HONS → ONSH.
Multifunctional metal–organic framework catalysts: synergistic catalysis and tandem reactions
Authors: Huang Yuan-Biao , Liang Jun , Wang Xu-Sheng , Cao Rong
Published: November 2016

Various active sites incorporated into metal–organic frameworks (MOFs) are suitable for synergistic catalysis and tandem reactions.
Effects of calcination and activation conditions on ordered mesoporous carbon supported iron catalysts for production of lower olefins from synthesis gas
Authors: Oschatz M. , van Deelen T. W. , Weber J. L. , Lamme W. S. , Wang G. , Goderis B. , Verkinderen O. , Dugulan A. I. , de Jong K. P.
Published: November 2016

Calcination and activation of CMK-3 supported iron catalysts for C2–C4 olefins production from syngas is investigated.
Restructuring of supported Pd by green solvents: an operando quick EXAFS (QEXAFS) study and implications for the derivation of structure–function relationships in Pd catalysis
Authors: Newton Mark A. , Brazier John B. , Barreiro Elena M. , Emerich Hermann , Adrio Luis A. , Mulligan Christopher J. , Hellgardt Klaus , Hii King Kuok (Mimi)
Published: November 2016

Aqueous ethanolic solvents rearrange Pd catalysts facilely toward a common state irrespective of starting Pd dispersion or support material.
Synthetic routes to iron chalcogenide nanoparticles and thin films
Authors: Matthews Peter D. , Akhtar Masood , Malik M. Azad , Revaprasadu Neerish , O'Brien Paul
Published: November 2016

This perspective summarises the key synthetic routes to iron chalcogenide thin films/nanoparticles by highlighting the key aspects that lead to control over phase/morphology.
The stepwise generation of multimetallic complexes based on a vinylbipyridine linkage and their photophysical properties
Authors: Toscani Anita , Jantan Khairil A. , Hena Jubeda B. , Robson Jonathan A. , Parmenter Emily J. , Fiorini Valentina , White Andrew J. P. , Stagni Stefano , Wilton-Ely James D. E. T.
Published: November 2016

A versatile bifunctional linker provides access to multimetallic assemblies with photophysical properties, which can be exploited to detect carbon monoxide.
Highly efficient nitrogen chelated ruthenium carbene metathesis catalysts
Authors: Duan Yulian , Wang Tao , Xie Qingxiao , Yu Xiaobo , Guo Weijie , Wang Jianhui , Liu Guiyan
Published: November 2016

Highly efficient nitrogen chelated ruthenium carbene metathesis catalysts containing an N-heterocyclic carbene (NHC) and a carbonyl group have been developed.
Dynamic neighbouring participation of nitrogen lone pairs on the chromogenic behaviour of trans-bis(salicylaldiminato)Pt(ii) coordination platforms
Authors: Hashimoto Takumi , Fukumoto Kanako , Le Ngoc Ha-Thu , Matsuoka Tatsuya , Kawamorita Soichiro , Komiya Naruyoshi , Naota Takeshi
Published: November 2016

The participation of neighbouring nitrogen lone pairs in the chromogenic control oftrans-bis(salicylaldiminato)Pt(ii) platforms was examined, using newly designed Pt analogues bearing salicylaldehyde hydrazone ligands.
Structural diversity and magnetic properties of six cobalt coordination polymers based on 2,2′-phosphinico-dibenzoate ligand
Authors: Wang Zhao-Xi , Wu Lin-Fei , Zhang Xuan , Xing Feifei , Li Ming-Xing
Published: November 2016

Six novel cobalt–carboxylate–phosphinate coordination polymers exhibit 1D chain, 2D networks and 3D frameworks. With difference on their structures, the compounds show remarkable magnetic behavior diversity containing spin canting, spin glass, and antiferromagnetic interaction.
H2S-tolerant oxygen-permeable ceramic membranes for hydrogen separation with a performance comparable to those of palladium-based membranes
Authors: Li Wenping , Cao Zhongwei , Cai Lili , Zhang Lixiao , Zhu Xuefeng , Yang Weishen
Published: November 2016

We propose a new method for hydrogen separation using an oxygen-permeable ceramic membrane, and achieve a high hydrogen separation rate comparable to those of Pd-based membranes and excellent stability under a H2S-containing atmosphere.
Recent developments in self-oscillating polymeric systems as smart materials: from polymers to bulk hydrogels
Authors: Kim Youn Soo , Tamate Ryota , Akimoto Aya Mizutani , Yoshida Ryo
Published: November 2016

As novel functional materials, we developed self-oscillating polymeric materials composed of synthetic polymers coupled with an oscillating chemical reaction, the so-called Belousov–Zhabotinsky (BZ) reaction.
Deconjugative alkylation/Heck reaction as a simple platform for dihydronaphthalene synthesis
Authors: Navaratne Primali V. , Grenning Alexander J.
Published: November 2016

A simple platform for carbocycle synthesis by Knoevenagel adduct deconjugative alkylation/“pairing” reaction is described.
Toward solid-phase peptide fragment ligation by a traceless-Ugi multicomponent reaction approach
Authors: Jobin Steve , Méjean Alexia , Galindo Sindy-Marcela , Liang Xinxia , Vézina-Dawod Simon , Biron Eric
Published: November 2016

Peptide fragments have been efficiently condensed by sequential on-resin Ugi four-component reaction and microwave-assisted backbone amide deprotection.
Histone-inspired biomimetic polymeric gene vehicles with excellent biocompatibility and enhanced transfection efficacy
Authors: Cui Peng-Fei , Zhuang Wan-Ru , Qiao Jian-Bin , Zhang Jia-Liang , He Yu-Jing , Luo Cheng-Qiong , Jin Qing-Ri , Xing Lei , Jiang Hu-Lin
Published: November 2016

Histone-inspired biomimetic polymeric gene vectors show great biocompatibility and enhanced transfection efficacy.
Platform of near-infrared light-induced reversible deactivation radical polymerization: upconversion nanoparticles as internal light sources
Authors: Ding Chunlai , Wang Jie , Zhang Wei , Pan Xiangqiang , Zhang Zhengbiao , Zhang Weidong , Zhu Jian , Zhu Xiulin
Published: November 2016

The use of a 980 nm light providing deep penetration power and high compatibility for weak bonds shows potential for bio-related applications.
Synthesis and chiroptical properties of a π-conjugated polymer containing glucose-linked biphenyl units in the main chain capable of folding into a helical conformation
Authors: Ikai Tomoyuki , Shimizu Syo , Awata Seiya , Kudo Tomoya , Yamada Takayuki , Maeda Katsuhiro , Kanoh Shigeyoshi
Published: November 2016

Naturally occurring ellagitannins provide us with inspiration for the development of a chiral π-conjugated polymer bearing glucose-linked biphenyl units in the main chain.
pH-Responsive polymers
Authors: Kocak G. , Tuncer C. , Bütün V.
Published: November 2016

This review summarizes pH-responsive monomers, polymers and their derivative nano- and micro-structures including micelles, cross-linked micelles, microgels and hydrogels.
Editorial: In celebration of Professor Barry M. Trost's 75th birthday
Authors: Breit Bernhard
Published: November 2016

This special issue is dedicated to Barry M. Trost, Tamaki Professor of Humanities and Sciences, on the occasion of his 75th birthday.
Abnormal change of melting points of gold nanoparticles confined between two-layer graphene nanosheets
Authors: Wang Gang , Wu Nanhua , Wang Jinjian , Shao Jingling , Zhu Xiaolei , Lu Xiaohua , Guo Lucun
Published: November 2016

A molecular dynamics simulation demonstrated that the melting temperature of gold nanoparticles confined in two-layer graphene nanosheets was indicated to decrease with nanoparticle size and a reasonable explanation is provided.
Gold nanoparticle-assisted polymerase chain reaction: effects of surface ligands, nanoparticle shape and material
Authors: Vanzha Ekaterina , Pylaev Timofey , Khanadeev Vitaly , Konnova Svetlana , Fedorova Valentina , Khlebtsov Nikolai
Published: November 2016

The concentration, shape, material, and surface functionalization effects of gold nanoparticles on PCR outcome have been studied with two PCR gene diagnostic models.
Preparation of oleic diethanolamide-capped copper borate/graphene oxide nanocomposites and their tribological properties in base oil
Authors: Li Wei , Cheng Zhi-Lin , Liu Zan
Published: November 2016

CuB/GO nanocomposites in base oil exhibited excellent friction properties compared with pure CuB nanoparticles, GO nanosheets and base oil.
Bioremediation of nitrate and Fe(ii) combined contamination in groundwater by heterotrophic denitrifying bacteria and microbial community analysis
Authors: Liu Ying , Feng Chuanping , Chen Nan , Sheng Yizhi , Dong Shanshan , Hao Chunbo , Lei Kang
Published: November 2016

The optimal condition range was determined for the simultaneous removal of nitrate and Fe(ii) in groundwater mediated by denitrifying Betaproteobacterial communities.
Plasmon-mediated photothermal conversion by TiN nanocubes toward CO oxidation under solar light illumination
Authors: Anjaneyulu Oruganti , Ishii Satoshi , Imai Tsubasa , Tanabe Toyokazu , Ueda Shigenori , Nagao Tadaaki , Abe Hideki
Published: November 2016

Titanium-nitride (TiN) nanocubes were decorated with platinum nanoparticles via a wet-chemistry route to yield TiN-supported Pt catalysts (Pt/TiN).
The role of zirconia in cobaltosic oxide catalysts for low-temperature CO oxidation
Authors: Du Fan , Wu Guisheng , Mao Dongsen , Lu Guanzhong
Published: November 2016

A series of Co3O4/ZrO2 catalysts for low-temperature CO oxidation was prepared, and then characterized by low-temperature N2 adsorption/desorption, XRD, TEM, XPS, UV-vis, CO-TPR, CO adsorption and CO2 desorption.
An unexpected reaction to methodology: an unprecedented approach to transamidation
Authors: Rakesh K. P. , Ramesha A. B. , Shantharam C. S. , Mantelingu K. , Mallesha N.
Published: November 2016

An unprecedented approach for the synthesis of disubstituted ureas from a cross coupling method using monosubstituted ureas, isocyanates and sodium hydride.
Diverting the phase transition behaviour of adipic acid via mesoporous silica confinement
Authors: Liu Shang , Ma Guixiang , Xie Shaolei , Jia Yongzhong , Sun Jinhe , Jing Yan
Published: November 2016

Phase transition regulation was achieved by imbibing adipic acid into mesoporous silica chambers, on the basis of pore size-dependent thermal behaviour.
Dual encapsulation of hydrophobic and hydrophilic drugs in PLGA nanoparticles by a single-step method: drug delivery and cytotoxicity assays
Authors: Español Laura , Larrea Ane , Andreu Vanesa , Mendoza Gracia , Arruebo Manuel , Sebastian Victor , Aurora-Prado María S. , Kedor-Hackmann Erika R. M. , Santoro Maria Ines R. M. , Santamaria Jesus
Published: November 2016

Dual drug encapsulation in biodegradable nanoparticles is always challenging and often requires strenuous optimization of the synthesis–encapsulation processes.
Nonprecious mixed oxide catalysts Co3AlO and Co2NiAlO derived from nanoflowerlike cobalt-based hydrotalcites for highly efficient oxidation of nitric oxide
Authors: Fan Ting , Dou Liguang , Zhang Hui
Published: November 2016

Nanoflowerlike Co3AlO-500 and Co2NiAlO-500 exhibit excellent NO oxidation performance upon abundant active sites Co3+/Ni3+–Oads through formation of bridged bidentate nitrate.