bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractDietary 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

AbstractMitsugumin 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

AbstractWe 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

AbstractMutations 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

AbstractThe 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

AbstractKenya 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

AbstractTo 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

AbstractMass 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

AbstractColorectal 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

AbstractRegional 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

AbstractS1 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

AbstractThe 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

AbstractGenomic 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

AbstractMajority 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.